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IntroductionCentral venous catheters (CVCs) are essential in modern healthcare. Insertion of a CVC promotes a hypercoagulable environment, in part through activation of the intrinsic coagulation pathway. We have previously shown that blood obtained from newly inserted CVCs demonstrates immediate coagulation activation, with differences between samples collected directly after insertion and after flushing of the catheter. The aim of this randomised trial is to compare early coagulation activation between four commonly used CVCs and to assess whether the different CVCs demonstrate different degrees of coagulation activation.Methods and analysisThis is a single-centre, randomised, parallel-group trial where adult patients (≥18 years) with a clinical indication for a two-lumen CVC will be eligible for inclusion. Participants will be randomised in a 1:1:1:1 ratio to receive one of four commercially available CVCs. The calculated sample size is 88 participants. Two blood samples will be obtained from each newly inserted CVC, the first obtained from the initial backflow of blood within seconds after insertion and the second after flush and discard. Samples will be analysed using rotational thromboelastometry with the non-activated thromboelastometry (ROTEM NATEM) and plasma-based coagulation assays. The primary outcome is the between-group comparison of the change in ROTEM NATEM clotting time between the two samples. Secondary outcomes include within-group and overall cohort comparisons of changes in clotting time. Additional secondary outcomes are between-group, within-group and overall cohort comparisons of changes in other ROTEM NATEM parameters, including clot formation time, alpha angle and maximum clot firmness, and changes in plasma-based coagulation markers, including prothrombin time–international normalised ratio, activated partial thromboplastin time, Factor VII, Factor XII and thrombin–antithrombin complex concentration. The results may help identify catheter materials that are less prone to activate coagulation and support in the selection and development of CVCs.Ethics and disseminationThis study has been approved by the Swedish Ethical Review Authority (#2022-00265-0). Written informed consent will be obtained from all participants before inclusion. The results will be published in a peer-reviewed journal and presented at scientific meetings.Trial registration numberNCT07014722.

Background A previous study on mechanical complications after central venous catheterisation demonstrated differences in complication rates between male and female operators. The objective of this subgroup analysis was to further investigate these differences. The hypothesis was that differences in distribution of predefined variables between operator genders could be identified. Methods This was a subgroup analysis of a prospective, multicentre, observational cohort study conducted between March 2019 and December 2020 including 8 586 patients ≥ 16 years receiving central venous catheters at four emergency care hospitals. The main outcome measure was major mechanical complications defined as major bleeding, severe cardiac arrhythmia, pneumothorax, arterial catheterisation, and persistent nerve injury. Independent t-test and χ 2 test were used to investigate differences in distribution of major mechanical complications and predefined variables between male and female operators. Multivariable logistic regression analysis was used to determine association between operator gender and major mechanical complications. Results Female operators had a lower rate of major mechanical complications than male operators (0.4% vs 0.8%, P  = .02), were less experienced ( P  < .001), had more patients with invasive positive pressure ventilation ( P  < .001), more often chose the internal jugular vein ( P  < .001) and more frequently used ultrasound guidance ( P  < .001). Male operators more often chose the subclavian vein ( P  < .001) and inserted more catheters with bore size ≥ 9 Fr ( P  < .001). Multivariable logistic regression analysis showed that male operator gender was associated with major mechanical complication (OR 2.67 [95% CI: 1.26–5.64]) after correction for other relevant independent variables. Conclusions The hypothesis was confirmed as differences in distribution of predefined variables between operator genders were found. Despite being less experienced, female operators had a lower rate of major mechanical complications. Furthermore, male operator gender was independently associated with a higher risk of major mechanical complications. Future studies are needed to further investigate differences in risk behaviour between male and female operators. Trial registration Clinicaltrials.gov identifier: NCT03782324. Date of registration: 20/12/2018.

Background Medical students navigate a complex landscape of digital tools with potential to enhance learning. The main objectives of the current study were to investigate which digital resources are being used, which background factors are associated with utilization, perceived advantages and disadvantages of different digital resources, and explore future directions. Methods Cross-sectional, nationwide, online 25-item multiple-choice question survey and one free-text question enabling qualitative data analysis. Medical students at all seven universities with medical school programs in Sweden were invited to participate. Data were collected October – December 2024. Results One thousand seven hundred sixty-six students responded to the survey, with an average response rate of 20.2% across sites. The five most frequently used digital resources were (percentage using at least on a weekly basis): University study platform (75.3%), videos (68.0%), flashcards (66.4%), student notes (53.4%) and external study platforms (47.3%). Flashcards were perceived to have a large to very large positive impact on development and maintenance of theoretical knowledge by 63.7% of students. Younger age (≤ 25 years) was strongly associated with higher use of flashcards (OR 1.98 (95% CI 1.54–2.54)) and generative artificial intelligence (AI) (OR 1.66 (1.29–2.15)), whereas having children at home was associated with more frequent use of videos (OR 2.32 (1.32–4.08)) and university digital platforms (OR 2.62 (1.26–5.45)), in multivariable logistic regression analyses. Most students (74.8%) reported finding their digital resources based on recommendations from more senior medical students. Perceived key advantages of digital resources in general were availability (90.9%), flexibility (80.6%), and more effective learning compared to traditional modalities (59.0%), while possible disadvantages included risk for distraction (49.6%) and uncertainty regarding reliability of content (45.4%). Qualitative data highlighted several areas of interest, including calls for universities and lecturers to provide high-quality, updated video material and flashcard decks tailored to the curriculum, and review and recommend third-party digital resources (e.g., YouTube channels). Conclusions Medical students extensively use digital resources, with perceived large positive learning effects and benefits. Several background factors influence usage patterns. These data may support institutions, program directors and teachers in their efforts to guide and improve use of digital learning tools in medical schools.

IntroductionCentral venous catheters are indispensable in modern healthcare. Unfortunately, they are accompanied by minor as well as major complications, leading to increased morbidity, mortality and costs. Immediate insertion-related complications (mechanical complications) have decreased due to the implementation of real-time ultrasound guidance, but they still occur and additional efforts to enhance patient safety are warranted. This study aims to investigate whether the use of a needle guide mounted on the ultrasound probe in subclavian catheterisations may decrease the number of catheterisations with >1 skin puncture (primary outcome).Methods and analysisThis is an investigator-initiated, non-commercial, randomised, controlled, parallel-group study conducted at Skåne University Hospital, Lund, Sweden. Adults (≥18 years) with a clinical indication for a subclavian central venous catheter and the ability to give written informed consent will be eligible for inclusion. Exclusion criteria include subclavian catheterisation deemed unsuitable based on the preprocedural ultrasound examination. Patients will be randomised to catheterisation by certified operators using a microconvex probe (long-axis, in-plane technique) with (n=150) or without (n=150) a needle guide. The ultrasound imaging from the procedures will be recorded and assessed by two reviewers individually. The assessors will be blinded for group affiliation. Secondary outcomes include the total number of skin punctures, mechanical complications, time to successful venous puncture, number of failed catheterisations and operator satisfaction with the needle guide at the end of the study period.Recruitment started on 8 November 2022 and will continue until the sample size is achieved.Ethics and disseminationThis study was approved by the Swedish Ethical Review Authority (#2022-04073-01) and the Swedish Medical Products Agency (#5.1-2022-52130; CIV-21-12-038367). The findings will be submitted to an international peer-reviewed journal.Trial registration numberNCT05513378, clinicaltrials.gov.

Background The right internal jugular vein is currently recommended for temporary central dialysis catheters (tCDC) based on results from previous studies showing a lower incidence of central vein stenosis compared to the subclavian vein. Data is however conflicting, and there are several advantages when the subclavian route is used for tCDCs. This prospective, controlled, randomised, non-inferiority study aims to compare the incidence of post-catheterisation central vein stenosis between the right subclavian and the right internal jugular routes. Methods Adult patients needing a tCDC will be included from several hospitals and randomised to either subclavian or internal jugular vein catheterisation with a silicone tCDC. Inclusion continues until 50 patients in each group have undergone a follow-up CT venography. The primary outcome is the incidence of post-catheterisation central vein stenosis detected by a CT venography performed 1.5 to 3 months after removal of the tCDC. Secondary outcomes include between-group comparisons of (I) the patients’ experience of discomfort and pain, (II) any dysfunction of the tCDC during use, (III) catheterisation success rate and (IV) the number of mechanical complications. Furthermore, the ability to detect central vein stenosis by a focused ultrasound examination will be evaluated using the CT venography as golden standard. Discussion The use of the subclavian route for tCDC placement has largely been abandoned due to older studies with various methodological issues. However, the subclavian route offers several advantages for the patient. This trial is designed to provide robust data on the incidence of central vein stenosis after silicone tCDC insertion in the era of ultrasound-guided catheterisations. Trial registration Clinicaltrials.gov; NCT04871568. Prospectively registered on May 4, 2021.

IntroductionCentral venous catheterisation is a common procedure in intensive care therapy and the use of central venous catheters is essential for treatment of many medical disorders. Although rare, central venous catheterisation is associated with mechanical complications that can be life-threatening if untreated. Real-time ultrasound guidance reduces the incidence of mechanical complications when compared with the anatomic landmark method. The purpose of this study is to determine the incidence of and potential risk factors associated with early mechanical complications of central venous catheterisation in an era where real-time ultrasound guidance has become clinical practice.Methods and analysisThis is a prospective, controlled, multicentre, observational study. All participating hospitals follow the same clinical guidelines for central venous catheterisation. Each central venous catheter insertion will be recorded in the common electronic chart system according to a recently revised template. An automated script-based search will identify all recorded central venous catheter insertion templates during the study period and relevant variables will be extracted. Outcome measures and independent variables are pre-defined in this study protocol. Multivariable and univariable logistic regression analysis will be used to determine associations and risk factors of mechanical complications.Ethics and disseminationThe Regional Ethical Review Board in Lund, Sweden has approved this study. The results will be submitted for publication in peer-reviewed medical journals and presented at national and international scientific meetings.Trial registration numberNCT03782324.

Statins, commonly used to treat hypercholesterolemia, have also been proposed as anti-cancer agents. The identification of a predictive marker is essential. The 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (HMGCR), which is inhibited by statins, might serve as such a marker. Thorough antibody validation was performed for four different HMGCR antibodies. Tumor expression of HMGCR (#AMAb90619, CL0260, Atlas Antibodies, Stockholm, Sweden) was evaluated in the Malmö Diet and Cancer Study breast cancer cohort. Statin use and cause of death data were retrieved from the Swedish Prescribed Drug Register and Swedish Death Registry, respectively. Breast cancer-specific mortality (BCM) according to statin use and HMGCR expression were analyzed using Cox regression models. Three-hundred-twelve of 910 breast cancer patients were prescribed statins; 74 patients before and 238 after their breast cancer diagnosis. HMGCR expression was assessable for 656 patients; 119 showed negative, 354 weak, and 184 moderate/strong expressions. HMGCR moderate/strong expression was associated with prognostically adverse tumor characteristics as higher histological grade, high Ki67, and ER negativity. HMGCR expression was not associated with BCM. Neither was statin use associated with BCM in our study. Among breast cancer patients on statins, no or weak HMGCR expression predicted favorable clinical outcome. These suggested associations need further testing in larger cohorts.

Purpose The increase in clinical trials with androgen receptor (AR)-targeting drugs emphasizes the need of clarifying the role of AR expression in different breast cancer subtypes. AR confers good prognosis in estrogen receptor positive (ER+) breast cancer, but its role in ER-negative (ER−) breast cancer is unclear. The aim of this study was to elaborate on previous findings of a differential prognostic role for AR depending on ER status, using breast cancer mortality (BCM) as endpoint, in a population-based cohort from the Malmö Diet and Cancer Study. Methods Immunohistochemical AR expression was assessed in 910 women with invasive breast cancer diagnosed 1991–2010, supplemented with clinicopathological information, vital status, and cause of death, with the last follow-up in December 2014 (median 10 years). Survival analyses according to AR status and AR/ER combinations were performed. Results AR expression was available for 671 tumors. AR+ ( n  = 573, 85%) was associated with favorable established tumor markers and lower BCM in univariable analysis, especially during the first 5 years following diagnosis [HR 0.4; 95% confidence intervals (CI) 0.2–0.7]. Multivariable analysis for short-term follow-up indicated higher BCM among patients with AR+ER− tumors (HR 3.5; 95% CI 1.4–9.1) than other AR and ER combinations. Conclusions AR expression added prognostic information to ER expression with respect to short-term prognosis. The worst prognosis was seen for patients with AR+/ER− tumors in short-term follow-up, supporting the pre-specified hypothesis. However, larger cohorts are needed for further characterization of the role of AR expression in ER− breast cancer.

Lipophilic statins purportedly exert anti-tumoral effects on breast cancer by decreasing proliferation and increasing apoptosis. HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway, is the target of statins. However, data on statin-induced effects on HMGCR activity in cancer are limited. Thus, this pre-operative study investigated statin-induced effects on tumor proliferation and HMGCR expression while analyzing HMGCR as a predictive marker for statin response in breast cancer treatment. The study was designed as a window-of-opportunity trial and included 50 patients with primary invasive breast cancer. High-dose atorvastatin (i.e., 80 mg/day) was prescribed to patients for 2 weeks before surgery. Pre- and post-statin paired tumor samples were analyzed for Ki67 and HMGCR immunohistochemical expression. Changes in the Ki67 expression and HMGCR activity following statin treatment were the primary and secondary endpoints, respectively. Up-regulation of HMGCR following atorvastatin treatment was observed in 68 % of the paired samples with evaluable HMGCR expression ( P  = 0.0005). The average relative decrease in Ki67 expression following atorvastatin treatment was 7.6 % ( P  = 0.39) in all paired samples, whereas the corresponding decrease in Ki67 expression in tumors expressing HMGCR in the pre-treatment sample was 24 % ( P  = 0.02). Furthermore, post-treatment Ki67 expression was inversely correlated to post-treatment HMGCR expression (rs = −0.42; P  = 0.03). Findings from this study suggest that HMGCR is targeted by statins in breast cancer cells in vivo, and that statins may have an anti-proliferative effect in HMGCR-positive tumors. Future studies are needed to evaluate HMGCR as a predictive marker for the selection of breast cancer patients who may benefit from statin treatment.