University Hospital of North Norway

Background/Objectives: Co-testing may improve cervical cancer prevention by stratifying women into groups with different absolute risks of CIN2+, CIN3+, and cervical cancer. We evaluated real-world co-testing with cervical cytology and a genotype-specific HPV E6/E7 mRNA assay targeting HPV16, HPV18, and HPV45 (PreTect SEE) in routine clinical practice. Methods: We conducted a retrospective, registry-based cohort study at the Department of Clinical Pathology, University Hospital of North Norway. Eligible co-test samples (liquid-based cytology with concurrent HPV mRNA testing, both with valid results) from routine screening, follow-up, and clinically indicated testing were identified from the laboratory information system and passively followed for worst histological outcome through December 2025. Outcomes were no biopsy/<CIN2, CIN2+, CIN3+, and cervical cancer. Results: Among 116,217 eligible co-test samples (mean age 43.9 years), cumulative risks were 4.4% for CIN2+, 1.5% for CIN3+, and 0.1% for cervical cancer. Baseline HPV mRNA positivity was 3.9%, and cytology was ASC-US+ in 12.2% of samples. Co-testing produced a clear stepwise risk gradient. Double-negative results (NILM/mRNA-; 86.7%) had very low risks (CIN3+ 0.2%; cervical cancer 0.02%). ASC-US+/mRNA- results (9.3%) showed intermediate risks (CIN3+ 4.1%; cervical cancer 0.2%). NILM/mRNA+ results (1.1%) showed substantially higher risks despite normal cytology (CIN3+ 13.0%; cervical cancer 0.5%). Double-positive results (ASC-US+/mRNA+; 2.8%) had the highest risks (CIN3+ 28.5%; cervical cancer 2.3%). Within NILM, mRNA positivity captured 42.7% of CIN3+ cases and 25.0% of cancers. Genotype-specific analyses showed highest risks for HPV16, followed by HPV18 and HPV45. Conclusions: Co-testing with cervical cytology and a 3-type HPV mRNA assay provided strong, clinically interpretable risk stratification and identified a small but high-risk subgroup among women with normal cytology. These findings support genotype-specific HPV mRNA testing as an adjunct to cytology in routine care.

Cancer-associated fibroblasts (CAFs) are influential elements of the tumor microenvironment with significant roles in tumor progression and therapy resistance. However, the effects that radiotherapy has on CAFs dynamics remain understudied. This study aimed to provide a non-invasive PET imaging approach to quantify radiation-induced changes in cancer-associated fibroblasts in preclinical tumor models. The FAP-specific radiotracer [18F]AlF-FAPI-74 was used to monitor CAFs dynamics following precision external beam radiotherapy (RT) in two syngeneic subcutaneous murine tumor models (LLC and CT26). Tumors were irradiated via two radiation regimens (1 × 12 Gy or 2 × 6 Gy), and dynamic PET/MR imaging was performed 7 days after RT. Additionally, the dynamics of FAP+ CAFs in tumors were quantified ex vivo via flow cytometry and immunohistochemistry. Tumor-targeted irradiation led to a significant reduction in tumor size. Uptake of [18F]AlF-FAPI-74 in subcutaneous tumors was low but significantly above muscle-background values. Quantification of standardized uptake values (SUVs) from static PET images revealed a twofold increase in the PET signal in LLC tumors irradiated with two fractions of medium-dose RT (2 × 6 Gy). Ex vivo analysis confirmed the low abundance of FAP+ cells in tumors and demonstrated similar RT-induced changes in CAF levels across the different models. Our findings suggest that CAFs constitute a relatively small cell population in subcutaneously transplanted tumor models, and that fractionated radiotherapy may induce a moderate increase in FAP+ cells in LLC tumors. Additionally, we demonstrated that [18F]AlF-FAPI-74 is a reliable biomarker for evaluating the number of FAP+ stromal cells in tumors and for addressing potential therapy-induced changes in CAFs.

Gaza has faced numerous military attacks that resulted in mass casualty incidents (MCIs). The ongoing genocide in Gaza has destroyed much of the health system, including killing and injuring of hundreds of health care workers (HCWs). Current thinking on the health system reconstruction lacks empirical data and local HCWs' perspectives. The study analyses locally driven innovations and lessons learned by HCWs who responded to MCIs between 2018 and 2021 to guide current and future planning of the reconstruction of the health system in Gaza. This was a qualitative study using online and face-to-face interviews with HCWs who responded to the Great March of Return and the 2021 Israeli military attacks. Transcripts and extensive notes from the interviews were recorded and analyzed on NVivo using thematic content analysis. We used the health system building blocks as themes for deductive analysis with a seventh place-based theme (Gaza-specific) to account for the context of Gaza and the MCIs. Problems faced by HCWs mostly related to the nature and complexity of traumatic injuries, shortages in HCWs, particularly specialist doctors, poor coordination among actors, duplication of services, and shortages of supplies and equipment. Locally driven innovations and solutions included establishing new services centers, opening and expanding training programs, starting new coordination bodies, and task shifting of staff and facilities. Lessons learned included strengthening training and employment opportunities for staff, enhancing emergency preparedness and capacities, maintaining coordination bodies, enhancing community engagement and strengthening the governance of the Ministry of Health. Reconstruction of Gaza's health system needs to be grounded in its political context and in the experiences of HCWs who have worked in and managed the system. Locally driven solutions and lessons learned can ensure that reconstruction serves as a vehicle for self-determination and sovereignty, rather than entrenching dependency.

The impact of surgical complications is substantial and multifaceted, affecting patients and their families, surgeons, and health care systems. Despite the remarkable progress in artificial intelligence (AI), there remains a notable gap in the prospective implementation of AI models in surgery that use real-time data to support decision-making and enable proactive intervention to reduce the risk of surgical complications. This scoping review aims to assess and analyze the adoption and use of AI models for preventing surgical complications. Furthermore, this review aims to identify barriers and facilitators for implementation at the bedside. Following PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines, we conducted a literature search using IEEE Xplore, Scopus, Web of Science, MEDLINE, ProQuest, PubMed, ABI, Embase, Epistemonikos, CINAHL, and Cochrane registries. The inclusion criteria included empirical, peer-reviewed studies published in English between January 2013 and January 2025, involving AI models for preventing surgical complications (surgical site infections, and heart and lung complications or stroke) in real-world settings. Exclusions included retrospective algorithm-only validations, nonempirical research (eg, editorials or protocols), and non-English studies. Study characteristics and AI model development details were extracted, along with performance statistics (eg, sensitivity and area under the receiver operating characteristic curve). We then used thematic analysis to synthesize findings related to AI models, prediction outputs, and validation methods. Studies were grouped into three main themes: (1) duration of hypotension, (2) risk for complications, and (3) decision support tool. Of the 275 identified records, 19 were included. The included models frequently demonstrated strong technical accuracy with high sensitivity and area under the receiver operating characteristic curve, particularly among studies evaluating decision support tools. However, only a few models were adopted routinely in clinical practice. Two studies evaluated the clinicians' perceptions regarding the use of AI models, reporting predominantly positive assessments of their usefulness. Overall, AI models hold potential to predict and prevent surgical complications as the validation studies demonstrated high accuracy. However, implementation in routine practice remains limited by usability barriers, workflow misalignment, trust concerns, and financial and ethical constraints. The evidence included in this scoping review was limited by the heterogeneity in study design and the predominance of small-scale feasibility studies, particularly for hypotension prediction. Future research should prioritize prospectively validated models that use other physiologic features and address clinicians' concerns regarding generalizability and adoption.

Klebsiella pneumoniae is a major cause of human infections and is frequently associated with antimicrobial resistance (AMR). Carriage of K. pneumoniae in the gut is a major risk factor for infection and a reservoir for the spread of high-risk clonal lineages and associated AMR determinants. Accurate detection of K. pneumoniae at the subspecies level is therefore essential to better understand K. pneumoniae gut colonization ecology and clonal dissemination. We analysed two recently developed bioinformatic tools, mSWEEP and StrainGE, for sequence type (ST) detection of K. pneumoniae in culture-enriched sweep metagenomes compared to single-colony whole-genome sequencing (WGS). We show that both mSWEEP and StrainGE perform highly accurate ST detection, concordant with culture in 46/49 and 44/49 samples with WGS-detected single STs, respectively, as well as in 2/3 samples with two WGS-detected STs. Within-sample ST diversity was detected in 19 and 15 samples by mSWEEP and StrainGE, respectively, highlighting a major advantage of these tools over conventional single-colony WGS. StrainGE could also reconstruct accurate phylogenetic relationships between strains of the same ST for 2/3 different STs tested. Additionally, assembly of the genomes provides better resolution of ST detection by mSWEEP. Together, our results show that both mSWEEP and StrainGE are accurate tools for the detection and analysis of K. pneumoniae STs from mixed bacterial samples.

Despite intriguing roles for the Succinate receptor (Sucnr1) in inflammation, few studies have explored its role in hematopoiesis. Here, we show that low SUCNR1 represents a marker for reduced overall and progression-free survival in acute myeloid leukemia (AML) patients. Succinic acid, which displays Sucnr1-dependent and independent effects, promotes disease in mouse models of pre-leukemic myelopoiesis, AML and AML xenografts, expressing low SUCNR1. In vivo global or hematopoietic deletion of Sucnr1 induces expansion of hematopoietic stem and progenitor cells (HSPC) and hematopoiesis, whilst Sucnr1-tomato+ HSPC display restricted engraftment potential. Mechanistically, activation of Sucnr1 counterbalances the stimulatory effect of intracellular succinate in HSPC and preserves HSPC transcriptional programs via control of S100a8/S100a9. Blocking S100a9 with tasquinimod rescues the defects of Sucnr1 knock-out mice, and combined with a potent Sucnr1 agonist shows therapeutic value in AML mice. In AML xenografts, single-cell RNA-sequencing reanalyses confirm SUCNR1 as a therapeutic vulnerability in patients. Together, Sucnr1 signaling restricts hematopoiesis at least partially through HSPC and via control of S100a8/S100a9. Its dysregulation emerges as contributor to malignancy that opens therapeutic avenues for AML patients.

Breast-conserving therapy requires a secure method to localize non-palpable lesions. The traditional and simple metal wire localization (WL) is challenged by more advanced and costly techniques that may have several advantages. We report the first European direct comparison between WL and SCOUT® Radar Localization (RL) comparing oncological and logistical benefits of implementing the new method in the treatment of non-palpable breast carcinomas including in situ lesions. We retrospectively analyzed 150 breast cancer surgeries performed immediately before and after WL was replaced by RL in our unit. The last 50 wire-guided surgeries were compared to the initial 50 radar-guided surgeries (cohort I, implementation phase) and to the subsequent 50 radar-guided surgeries (cohort II, routine phase). All lesions and markers were successfully removed in all groups. No procedure-specific complications were registered. Of the 50 patients in the WL group, 8% needed redo surgery due to positive margins, compared to 4% in the RL groups (not statistically different). The histological margin was similar between the groups. The median time consumption during surgery was reduced by 26.5min after establishing the radar localization method (p=0.022). The resected tissue corresponded better with the marked area in the breast in the RL group (p=0.026), as evaluated by a more central placement of the marker. Radar localization of breast carcinomas is safe for women with non-palpable breast carcinomas including in situ lesions. The method reduces time consumption in the operating room and may give better surgical precision.

Healthcare professionals often face tension between caregiving values and systemic demands for efficiency and economic stability. While caregivers focus on patient well-being, hospital leaders must ensure resource and staff management-roles that can appear contradictory. This study explores how both caregivers and leaders in a large Norwegian hospital experience meaning in their work, aiming to identify shared ground for healthcare engagement. Drawing on Hartmut Rosa's resonance theory and Tatjana Schnell's research on meaning in life, we examine how professional experiences foster or hinder resonance-a mode of being characterized by mutual responsiveness and transformation. Twelve semi-structured interviews were conducted with nurses, doctors, and leaders using a guide informed by resonance theory. Data were analyzed thematically in a multidisciplinary team. Four themes emerged: (1) healthcare as a demanding yet meaningful profession, (2) organizational challenges, (3) patient relationships, and (4) teamwork and collegial support. Across roles, participants described systemic pressures that threaten meaningful engagement, but also highlighted moments of deep resonance-particularly in patient care, collaboration, and learning. Resonance and meaning are sustained when work aligns with moral purpose and supports relational and reflective engagement. Both caregivers and leaders seek meaning in their roles, often through shared values and relationships. These findings underscore the need for organizational structures that allow space for resonance, rather than accelerating alienation through excessive control and restructuring. Caring for meaning represents common ground for caregivers and leaders. A resonance-informed healthcare leadership might strengthen both staff well-being and quality of care.

Abstract Background: Integrated care fundamentally depends on timely awareness and access to distributed patient records. However, patients with multimorbidity navigate complex, circular pathways, creating information fragmentation that compromises safety and efficiency. Current Health Information Systems often lack robust frameworks for inter-organizational Data Management (DM). This study aims to design a conceptual information architecture framework to resolve systemic gaps in awareness, access, and the integration of the patient’s voice. Methods: Applying Design Science Research (DSR), this study synthesizes rigor from a scoping review with relevance from a longitudinal analysis of 14 multimorbid patients (1954–2024). A representative 19-year user scenario was validated by clinical expertise, and along with root-cause and stakeholder analysis, systemic failures in information logistics were explicated. High-level functional and non-functional requirements were iteratively derived, foregrounding Information Governance (IG), DM, and Security and Privacy as essential constraints. Results: The resulting artifact is a prescriptive information-centric architecture framework (meta-artifact). The layered, modular design decouples metadata, clinical codes, and location pointers into lightweight information tokens, enabling a paradigm shift from physical record replication to governed virtual access. This structure separates concerns across user interaction, pathway logic, and secure storage, providing the structural flexibility required for complex inter-organizational DM. Critically, Health Information Quality (HIQ) is positioned as the functional mechanism to operationalize DM, enforcing structural imperatives (R6–R7) for data accuracy, currency, and contextual relevance. These mechanisms directly mitigate empirically identified failures such as data duplication (F1, F2) and coordination delays (F4). Conceptual feasibility was demonstrated through an acute care transition and discharge use case. Conclusions: This study contributes reusable prescriptive design knowledge, validating the utility of architectural frameworks in solving socio-technical information logistics problems. By embedding Security and Privacy, and IG and DM as authoritative vertical pillars, and operationalizing DM through HIQ, the architecture facilitates high-quality information assets to support inter-organizational information logistics, data-driven opportunities, proactive awareness, and on-demand virtual access, while sustaining interprofessional trust and collaboration. The standards- and vendor-neutral design ensures international relevance and accommodates emerging technologies, such as blockchain and AI. This framework provides a verifiable blueprint in which clinical reasoning and patient-centric pathways guide information logistics.

BackgroundThe digital divide in health has rapidly expanded during and after the COVID-19 pandemic, with fragmented understanding and an unclear implementation process, for the formal integration of digital health into the healthcare system, which challenges actionable policy development.MethodsThis critical interpretive synthesis (CIS) of the literature aimed to capture the complexity of the digital divide in health. This began with a scoping review of literature published between 2013 and 2023 describing the digital divide in health within the WHO's European Region, in Web of Science, Medline (via Ovid), PsycInfo (via Ovid), and Sociological (via ProQuest). Three sets of two reviewers independently conducted the selection, and all contributed to the synthesis process.ResultsOf 4,967 original articles identified, 49 articles were included for review. Results revealed a synthesizing argument that the digital divide should be considered as more of a dynamic, entangled, and reciprocal collection of “areas” of phenomenon affecting service users, rather than “levels”. Results describe the three synthetic constructs that describe this synthesizing argument.ConclusionFindings suggest that digital health solutions should respectfully consider the pace of human healing, long-term user engagement and adaptability. We call for the importance of inter- and multidisciplinary collaboration to ensure effective and context-sensitive implementation in future studies.