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The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 and disease recovery in convalescent patients, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. Core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.

How disturbances of B cell development provoke adult B acute lymphoblastic leukemia (B-ALL) remains poorly understood. Here we describe Irf4–/– mice as prone to developing B-ALL with age. Irf4–/– pro/preB cells exhibited impaired differentiative but enhanced proliferative potential in vitro and accumulated in spleens of healthy Irf4–/– mice, suggesting reduced adherence to the IL-7 providing bone marrow niche. Thus selected, pro/preB cells transformed acquiring proliferative IL-7 independency through Jak3 gain-of-function mutations. Targeting JAK signaling with Ruxolitinib in vivo prolonged survival of mice bearing established Irf4–/– leukemia. Intriguingly, organ infiltration including leukemic meningeosis was selectively reduced without affecting blood blast counts. As low IRF4 expression and JAK3 mutations also characterize a subpopulation of Ph-like B-ALL in adult humans, our results imply Irf4–/– mice as a suitable model for investigating preleukemic conditions in adults. Using this model, we identified an unexpected effect of Ruxolitinib treatment in B-ALL.

Background Nurses are the key professionals in the introduction, implementation, and use of technology in clinical practice. A lack of technical expertise and technological understanding poses a challenge to the quality of health services and possibly to the safety, dignity, and quality of life of patients. Therefore, possessing technological literacy upon completing nursing baccalaureate studies is essential. However, no previous scoping review has mapped the existing studies of technological literacy in nursing education. Objectives To map and assess the published studies on technological literacy in nursing education and to identify how educational institutions operationalize, teach, measure, and maintain students' technological literacy throughout their educational programs. Design A scoping review was conducted using the methodological framework of Arksey and O'Malley. The reporting was guided by the PRISMA extension for Scoping Reviews. Methods A comprehensive systematic search of the MEDLINE, EMBASE, PsycINFO, ERIC, and CINAHL was performed for studies published from January 2008 through March 2020. Two authors independently assessed eligibility and extracted data. The reference lists of the included studies were also examined. Results The review included 28 papers from 27 studies. Three thematic groupings with their respective subgroups were identified among the included papers: 1) the acquisition (simulated electronic documentation, diversified learning methods, and evaluation learning focus), 2) the measurement (digital/computer literacy/competence, nursing informatics competence, technology acceptance, and students' interests and preferences in technology), and 3) the maintenance (follow-up evaluation) of technological knowledge and skills. Conclusions Pedagogical models designed to teach an entire process for the acquisition, measurement, and maintenance of technological literacy are lacking. Studies are needed that bring technological competencies to a higher level, including problem-solving and critical thinking. Educators' competencies should be enhanced. Educational institutions need to ensure the readiness of future nurses for a technology-enriched environment by providing the necessary knowledge in technological literacy. “Tweetable abstract” Due to the importance of technological literacy to the nursing profession, educational institutions must ensure that it is taught to nursing students.

Research on the digital divide has moved beyond connectivity to skills and usage disparities. Yet for many older people lack of connectivity remains a challenge, and for those who do have access, skills and usage remain an issue. We report findings of an in-depth qualitative study of older people's perceptions of online communications and also their actual experiences. Findings indicate that older people who are already socially well connected benefit from online communication more than those who are not. The final version of this research has been published in Information Society. © 2017 Taylor & Francis

Purpose To present an emerging innovative care model that supports participation and thriving by older adults in residential care, by introduction to new technology and mobilizing volunteer services. Design Qualitative, exploratory study, introducing tablet computers to 15 older adults in two municipalities. Methods The intervention encompassed weekly workshops over the course of 1 year with volunteer adolescents as personal tutors. Observations of workshops, interviews with nurses, and repeated semistructured interviews with older adult participants eliciting their perspective on use, experiences, perceived usefulness, and overall evaluation of the intervention. Findings A model of four components is suggested to support participation and thriving by older adults in residential care: (a) simplified tools: iPad—technology relatively easy to use; (b) person-centered process: one-to-one tutoring following each individual's own pace; (c) young volunteers to teach technology, establishing an intergenerational arena; and (d) being mindful of driving forces that encourage use and learning. We found that all kinds of use and all levels of mastery generated a sense of pride that supported thriving and enjoyment. Conclusions These findings support the use of new technology and use of volunteer services for sustaining thriving in older adults. The person-centered approach stimulates use of the tablet, and participants showed enjoyment, more social participation, and reported subjective experiences of thriving. Clinical Relevance Innovative models of care that prevent (or postpone) functional decline and support thriving in older adults are highly sought after in health care. A model that systematically involves volunteer services comes with potentials to alleviate nurses’ workload, and then the intervention is seen as a manageable and low-cost initiative in residential care.

The study explored how 125 older patients and 92 next of kin experienced and assessed continuity in long-term home health care. Data were collected by means of structured interviews. A majority of the patients indicated that having a high number of health care personnel involved in their care was not problematic. For patients, informed and skilled health personnel along with knowing the visiting personnel may compensate for a high number of personnel. For next of kin, accepting a high number of personnel was related to the carers being informed about the patient’s situation. This study indicates that, in terms of patient satisfaction, the overall quality of care is more important than the number of people providing the care.

In 2013, cancer immunotherapy was selected as the breakthrough of the year by Science’s editors and monoclonal antibody therapy is considered one of its most successful tools. When castration-resistant prostate cancer (PCa) disease progresses and despite androgen deprivation treatment, it typically metastasizes, leading to poor patients’ prognosis and survival. In this case, immunotherapy represents the only chance of treatment. In a previous study carried out by our team on the role of cytoplasmic PML1 in the context of epithelial to mesenchymal transition (EMT) in PCa2, we identified a new promising PCa target for antibody-based therapy. Our target, of which we cannot disclose the name for patenting reasons and that we will further refer to as Protein-X, is a type 1 transmembrane protein that is specifically expressed by PCa cell. Transcriptome profiling obtained using Nanostring technology with a cancer progression panel showed that the knockdown of Protein-X leads to an upregulation of the epithelial EMT marker E-cadherin in PCa cells, suggesting its role in the process. Furthermore, the clinical value of Protein-X as a diagnostic and/or prognostic biomarker of invasive and aggressive PCa, is also being investigated by a histopathologist using immunohistochemistry analysis of Protein-X’s expression on tissue microarrays (TMAs). To develop a monoclonal antibody-based therapy against Protein-X, mouse monoclonal antibodies (mAbs) were generated using hybridoma technology. MAbs-producing hybridomas were sequenced and purified mAbs were tested for their specificity by flow cytometry, immunofluorescence, ELISA and immunoblotting assays. Using in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) reporter assay, we show that the antibodies mediate cell cytotoxicity. This result will be further investigated in vivo using a xenograft mouse model. Future experiments will focus on designing and generating chimeric antigen receptor (CARs) modified adoptive T-cell targeting of Protein-X-expressing tumor cells and bispecific antibodies. In summary, we aim to develop an anti-Protein-X antibody-based therapy against invasive prostate cancer, which will potentially represent a new tool to target aggressive PCa responsible for cancer metastasis and poor prognosis in PCs patients. Citation Format: Anna Di Biase, Tarik Regad, Jayakumar Vadakekolathu, Desmond Powe, Hans-Martin Jäck, Edith Roth. Generation of monoclonal antibodies against a newly identified target for invasive prostate cancer and their use in the development of an antibody-based targeting therapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B152.

Aim To explore continuity of care from a manager’s perspective: How do managers understand the concept of continuity of care and how do they assess continuity of care in home health-care? How do managers work to ensure continuity of care when managing care provision for patients in their homes? Background Continuity of care is considered a prerequisite for service quality. Managers can influence continuity of care through managing day-to-day work. Methods Semi-structured interviews of a purposive sample of 16 managers from 12 municipal units. Theory-driven and data-driven analysis was applied. Results Ideally, to promote continuity of care, the number of carers should be limited. Yet, in practice, discontinuity of care was accepted as a working compromise. The managers faced two paradoxes: the continuity ideal vs. the practicalities of home health-care, and caring for patients vs. caring for staff. Conclusions The managers were forced to prioritize, in conflict with ideals or professional standards, patients’ wellbeing or the wellbeing of the staff. Ensuring continuity of care for all patients did not seem feasible. Implications for nursing management The study highlights management paradoxes: possible unintended consequences of prioritizing needs for continuity of care should be objects of reflection in care management.

Objective. To explore the first-line leaders’ role in quality work in long-term care in Norway, in order to determine how that work is related to such success characteristics as leadership, staff, patients, performance, information and information technology. Design. Cross-sectional telephone survey. The text was analysed using content analysis. Setting. Thirty-two Norwegian municipalities stratified according to region and population size. Participants. Sixty-four first-line leaders in nursing homes and home-based care. Main outcome measure. The clinical microsystem approach is used as a framework by defining and designing measureable variables. Results. Thirty-six leaders described how they initiated and motivated employees to be active in quality work; the remaining leaders indicated that they played a passive role. The first-line leaders played a key role in implementing national quality policies and regulations. The quantity of other success characteristics was low. Conclusions. The municipalities delegated the responsibility of implanting national policies to the first-line leaders. Missing were key quality success criteria such as macro- and meso-perspectives for the municipality as a whole and co-operation with other leaders in the organization and fostering of relevant learning. Quality work was fragmented rather than comprehensive and systematic.

Aims. The present study explores how community nurses addressed patient care in the EPR and the comprehensiveness of their documentation. Background. The need for comprehensive nursing documentation in home health care is considerable and quality is regarded as a prerequisite for continuity of care. Documentation according to the nursing process is considered to be of good quality due to its logical structure. Nurses in home health care face different challenges than nurses in institutionalised care because of long-term patient situations and a focus on chronic illness rather than acute disease. Design. Retrospective study. Method. The study was performed on a sample of 91 patient records. Data were analysed in three phases: (1) systematising the unstructured text, (2) structuring the text according to the nursing process and (3) assessing the comprehensiveness using a validated instrument. Results. The home care nurses documented patient care chronologically along a time axis rather than using a logical structure according to the nursing process. The documentation reflected today’s overall emphasis on patient participation, as more than 70% of the notes on nursing status were connected to subjective nursing status. Paradoxically, the nurses showed a lack of attention to the patients’ ability to communicate. Only two of 264 documented nursing diagnoses were connected to communication. The comprehensiveness of the documentation, however, was incomplete. Conclusions. Home health care nurses are attentive to patient participation but fail to address patients’ needs with regard to communication. The documentation is incomplete when assessed according to the steps of the nursing process. A question that arises is whether the nursing process may be a limitation for the quality of the nursing documentation. Relevance to clinical practice. The study contributes to identifying areas of improvement in documentation by nurses in home health care.

Progressive loss of hip containment attributable to dysplasia epiphysealis hemimelica of the right proximal femur and macrodactyly of the right second toe was diagnosed and monitored by radiographs and magnetic resonance imaging in a 7-year-old boy. The patient had early surgical correction including shortening osteotomy of the hypertrophic toe and partial resection of the involved superolateral femoral head-neck junction combined with a Pemberton-like acetabuloplasty. This treatment restored containment and function. At 4 years followup, the femoral head remained contained and the patient was participating fully in the activities of daily life for his age-group. A review of the literature suggests monitoring the hip with magnetic resonance imaging may allow early identification of a hip at risk for loss of containment. This treatment may save the hip from severe deformity and early secondary osteoarthritis.

Operationsziel Stabiles, belastungsfahiges und bewegliches Huftgelenk. Indikationen Unbehandelte luxierte Huftgelenke bei uber sechs Monaten alten Sauglingen. Persistierend instabiles Gelenk bei junger als sechs Monaten alten Sauglingen nach achtwochigem Repositions- und Retentionsversuch. Kontraindikationen Beidseitige Luxation bei Arthrogryposis multiplex. Hohe Huftluxation mit Inkongruenz der Gelenkpartner bei Jugendlichen und Erwachsenen. Operationstechnik Anterolateraler Zugang und Darstellung des Intertrochantergebiets. Fenestrierung der Gelenkkapsel. Resektion des Ligamentum teres und des Pulvinars, partielle Resektion des Ligamentum transversum und der Iliopsoassehne, Reposition unter Innenrotation und Abduktion. Fixierung des Huftkopfes in Repositionsstellung mit einem durch den Schenkelhals in das Azetabulum gebohrten Kirschner-Draht. Intertrochantare Osteotomie und Fixierung der Fragmente in Neutralstellung der Gliedmase mit zwei Kirschner-Drahten. Becken-Bein-Gipsverband mit Fusteil fur sechs Wochen in Neutralstellung des Beins. Nach sechs Wochen Entfernung des Gipsverbandes und aller Kirschner-Drahte. Keine Orthese. Bei persistierender Pfannendysplasie Azetabuloplastuk empfohlen. Ergebnisse 48 Huftgelenke wurden zwischen 1981 und 1995 operiert; durchschnittliche Nachuntersuchungszeit 8,3 Jahre (sechs Monate bis 18 Jahre). Die Nachuntersuchungsergebnisse aller Patienten wurden nach Barrett et al. bewertet. Es kam zu keiner Reluxation. Bei 32 Patienten fanden sich ausgezeichnete und gute, bei sieben mittelmasige und bei weiteren sieben schlechte Ergebnisse. Bei Operationen bis zum sechsten Lebensmonat traten keine, bei Eingriffen zwischen dem sechsten und zwolften Lebensmonat zwei Huftkopfnekrosen auf; bei nach dem zwolften Lebensmonat operierten Kindern kam es zu vier Huftkopfnekrosen. Die besten klinischen und radiologischen Gesamtergebnisse waren bei Eingriffen bis zum sechsten Lebensmonat zu verzeichnen. Die klinischen und radiologischen Gesamtergebnisse verschlechterten sich kontinuierlich bei Operationen nach dem sechsten Lebensmonat.

Aim To provide a method for assessing the degree of interpersonal continuity adapted to context and to measure and assess the degree of interpersonal continuity for long-term recipients dependent on daily home health care. Background Interpersonal continuity is important to the quality of care for long-term dependents. In high-frequency home healthcare services where patients receive daily care from many nurses or other health personnel over time, interpersonal continuity may be difficult to attain. Design A cross-sectional study with a descriptive design. Methods Information concerning 79 patients receiving long-term frequent care was collected during four weeks in a maximum variation sample of Norwegian municipalities, from January 2009–May 2010. We measured interpersonal continuity objectively using indices of dispersion and the next-day sequence of health personnel. For each measure, we computed the highest feasible level of continuity that could be attained in this home healthcare context given a standard shift plan. This level was then used as benchmark against which the actual level of continuity was assessed. Results Patients received on average 51 visits from a mean of 17 different carers during four weeks. The results revealed a low degree of interpersonal continuity in practice, far below what was feasible according to the benchmarks. Conclusion High-frequency home health care was characterized by interpersonal discontinuity, but with potential for improvement. Objective measures of interpersonal continuity, when the benchmark is adapted to the context, are useful tools for planning and surveying continuity of care.