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Abstract Background Knee osteoarthritis (KOA) presents a prevalent orthopedic condition causing substantial impairment in the quality of life and imposing a significant societal and economic burden. Mesenchymal stromal/stem cells (MSCs), known for their regenerative properties and immunomodulatory effects, have emerged as a promising therapeutic avenue in regenerative medicine. Despite MSCs' therapeutic potential, their precise mechanisms of action in KOA remain underexplored. Methods Conducted as a randomized, open-label clinical trial, 20 patients will be enrolled, with 10 in the intervention group and 10 in the control group. The primary focus will be to explore the molecular mechanisms associated with MSC therapy. Biomarkers and gene expressions related to cartilage metabolism, inflammation, immune modulation, and pain in the synovial fluid, blood, and tissue samples will be analyzed. Patients will undergo pre- and post-treatment evaluations using patient-reported outcome measures (PROMs) and comprehensive clinical assessments. Discussion This is an exploratory study with the goal to provide comprehensive insights into the therapeutic effects of MSCs on a molecular level, potentially paving the way for optimized and more effective MSC-based therapies in the management of KOA, as well as furthering the development of novel treatment strategies. Trial registration ClinicalTrials.gov, NCT06078059. Registered on 5 October 2023.

Protein- and peptide-based proton-conducting biomaterials have been touted as particularly promising for bioelectronics applications because of their advantageous chemical and physical characteristics, typically excellent biocompatibilities, and readily understood electrical properties. Within this context, our laboratory has previously discovered and systematically investigated bulk proton conduction for a unique family of cephalopod structural proteins called reflectins. Herein, we leverage a combination of experimental and computational methodologies to investigate the bulk electrical properties of hierarchically nanostructured films self-assembled from a previously reported truncated reflectin variant. Our findings indicate that the truncated reflectin variant exhibits protonic conductivities and associated figures of merit on par with those reported for both full-length reflectins and other proteinaceous proton-conducting materials. The combined studies enhance current understanding of reflectins’ functional properties within the framework of bioengineering and bioelectronics applications and may ultimately facilitate the development of other protein- and peptide-based conductive biomaterials.

IntroductionPsychiatric comorbidities have proven a consistent challenge. Recent approaches emphasize the need to move away from categorical descriptions of symptom clusters towards a dimensional view of mental disorders. From the perspective of phenomenological psychopathology, this shift is not enough, as a more detailed understanding of patients’ lived experience is necessary as well. One phenomenology-informed approach suggests that we can better understand the nature of psychiatric disorders through personalized network models, a comprehensive description of a person’s lifeworld in the form of salient nodes and the relationships between them. We present a detailed case study of a patient with multiple comorbidities, maladaptive coping mechanisms, and adverse childhood experiences.MethodsThe case was followed for a period of two years, during which we collected multiple streams of data, ranging from phenomenological interviews, neuropsychological assessments, language analysis, and semi-structured interviews (Examination of Anomalous Self Experience and Examination of Anomalous World Experience). We analytically constructed a personalized network model of his lifeworld.ResultsWe identified an experiential category “the crisis of objectivity” as the core psychopathological theme of his lifeworld. It refers to his persistent mistrust towards any information that he obtains that he appraises as originating in his subjectivity. We can developmentally trace the crisis of objectivity to his adverse childhood experience, as well as him experiencing a psychotic episode in earnest. He developed various maladaptive coping mechanisms in order to compensate for his psychotic symptoms. Interestingly, we found correspondence between his subjective reports and other sources of data.DiscussionHernan exhibits difficulties in multiple Research Domain Criteria constructs. While we can say that social sensorimotor, positive valence, and negative valence systems dysfunctions are likely associated with primary deficit (originating in his adverse childhood experience), his cognitive symptoms may be tied to his maladaptive coping mechanisms (although, they might be related to his primary disorder as well).

Sofoklejeva Antigona ima bogato in edinstveno, več kot stoletno zgodovino uprizarjanja na slovenskih poklicnih odrih. Začela se je z neuspelo predstavo pod taktirko Hinka Nučiča na odru ljubljanske Drame leta 1912 in nadaljevala s priljubljeno postavitvijo Frana Lipaha v istem gledališču na predvečer druge svetovne vojne. Po vojni je primat pri uprizarjanju te tragedije prevzelo Slovensko ljudsko gledališče Celje (tedaj se je imenovalo Mestno gledališče Celje); vse do leta 2013 je bilo celo edino slovensko poklicno gledališče, ki jo je uprizarjalo, prvič leta 1956 (r. Herbert Grün), nato še leta 1973 (r. Franci Križaj), nazadnje pa leta 2011 (r. Anđelka Nikolić). Glavni razlog za to nenavadno odsotnost Sofoklejeve Antigone na drugih slovenskih poklicnih odrih je bila najverjetneje izjemna priljubljenost Smoletove drame z istim naslovom, ki je bila v tem času uprizorjena kar osemkrat, še dodatno pa so Sofokleja izrivale tudi (redkejše) uprizoritve drugih modernih Antigon (Dušan Jovanović, Miro Gavran, Janusz Głowacki). Zadnje desetletje je vendarle prineslo preporod zanimanja za Sofoklejevo različico (in obenem tudi zaton zanimanja za uprizarjanje Smoleta, kar pritrjuje naši spekulaciji o njunem programskem konkuriranju). Po kritiško dobro sprejeti celjski uprizoritvi v režiji Anđelke Nikolić, sta bili leta 2013 prvič na sporedu dve uprizoritvi, prva v Mestnem gledališču ljubljanskem (bralna uprizoritev, r. Ira Ratej) in druga v Lutkovnem gledališču Ljubljana (r. Marko Čeh). Nazadnje, leta 2017, pa se je Antigona v udarnem slogu končno vrnila tudi v ljubljansko Dramo (r. Eduard Miler).

Abstract Disordered protein sequences can exhibit different binding modes, ranging from well-ordered folding-upon-binding to highly dynamic fuzzy binding. The primary function of the intrinsically disordered region of the antitoxin HigA2 from Vibrio cholerae is to neutralize HigB2 toxin through ultra-high-affinity folding-upon-binding interaction. Here, we show that the same intrinsically disordered region can also mediate fuzzy interactions with its operator DNA and, through interplay with the folded helix-turn-helix domain, regulates transcription from the higBA2 operon. NMR, SAXS, ITC and in vivo experiments converge towards a consistent picture where a specific set of residues in the intrinsically disordered region mediate electrostatic and hydrophobic interactions while “hovering” over the DNA operator. Sensitivity of the intrinsically disordered region to scrambling the sequence, position-specific contacts and absence of redundant, multivalent interactions, point towards a more specific type of fuzzy binding. Our work demonstrates how a bacterial regulator achieves dual functionality by utilizing two distinct interaction modes within the same disordered sequence.

Extracellular nanoparticles (EPs) are a subject of increasing interest for their biological role as mediators in cell–cell communication; however, their harvesting and assessment from bodily fluids are challenging, as processing can significantly affect samples. With the aim of minimizing processing artifacts, we assessed the number density (n) and hydrodynamic diameter (Dh) of EPs directly in diluted plasma and blood using the following recently developed technique: interferometric light microscopy (ILM). We analyzed 613 blood and plasma samples from human patients with inflammatory bowel disease (IBD), collected in trisodium citrate and ethylenediaminetetraacetic acid (EDTA) anticoagulants, and 163 blood and plasma samples from canine patients with brachycephalic obstructive airway syndrome (BOAS). We found a highly statistically significant correlation between n in the plasma and n in the blood only in the human (i.e., but not canine) blood samples, between the samples with trisodium citrate and EDTA, and between the respective Dh for both species (all p < 10−3). In the human plasma, the average was 139 ± 31 nm; in the human blood, was 158 ± 11 nm; in the canine plasma, was 155 ± 32 nm; and in the canine blood, was 171 ± 33 nm. The differences within species were statistically significant (p < 10−2), with sufficient statistical power (P > 0.8). For , we found no statistically significant differences between the human plasma and blood samples or between the samples with trisodium citrate and EDTA. Our results prove that measuring n and Dh of EPs in minimally processed fresh blood and in diluted fresh plasma by means of ILM is feasible for large populations of samples.

In the second half of the 1980s, Tine Hribar developed a distinctive interpretation of Sophocles’s Antigone, which he presented in 1991 in the monograph Tragična etika svetosti (The tragical ethics of sacredness). Here he developed an original concept of the sacred, on which he built an ethical system that has become – particularly through its determined defense of the so-called sanctity of the dead – a cornerstone of the Slovene reconciliation project. This paper deals with some of the fundamental problems that stem from Hribar’s enigmatic definition of the sacred as “the world itself in itself,” showing that, in the conclusions Hribar draws from that definition, the clear distinction between being and life is lost. The central aporia of the Tragična etika svetosti is also closely intertwined with other problematic dimensions of the work that are analysed in the paper: the unfounded appropriation of the ethical characteristics of traditions from which he distances himself in principle; the unreflecting distinction between being and action in relation to the sacred; and not least, the unexplained oscillation between vitalism and Antigone’s ideal of self sacrifice.

Background Biomaterials augmented with Bone Marrow Aspirate Concentrate (BMAC) are becoming increasingly utilized in the cartilage treatment. However, the potential role of cellular parameters in the intraoperatively applied BMAC have yet to be elucidated. Purpose (A) To evaluate clinical outcomes and safety of a combined single-step approach with scaffolds (fibrin glues, collagen gels, collagen-hydroxyapatite membrane) and filtered Bone Marrow Aspirate (fBMA) for the treatment of osteochondral lesions of the talus (OLTs). (B) To identify significant factors for postoperative improvements, considering cellular parameters as potential predictors. Methods All the patients operated on due to OLTs by the combination above were selected from the hospital registry database (35 pts, years 16–55, and minimally 1 year follow-up). Treatment outcomes were followed clinically with Patient-reported outcome measures (PROMs), and by pursuing serious adverse events (SAE) and graft failures (GF). Cellular parameters of the injected fBMA were determined. Pre- and postoperative PROMs values were compared to evaluate postoperative improvements. Multivariable regression models were applied to identify potential factors (demographics, medical history, joint and lesion characteristics, scaffold type, surgical and cellular parameters) that predict the treatment outcomes. Results At the mean follow-up of 32.2 (12.5) months, all Foot and Ankle Outcome Score (FAOS) and European Quality of Life in Five Dimensions Three-Level (EQ-5D-3 L) values improved significantly. 4 (11%) SAE (3 arthrofibrosis, one hardware removal), and 3 (9%) GF occurred. Female gender and concomitant procedures were the main negative predictors for postoperative outcomes. The number of fibroblast colony forming units (CFU-F) or their proportion among total nucleated cells (CFU-F/TNC) were positively correlated with the improvements of some PROMs. Conclusions Scaffolds augmented with fBMA proved as an adequate and safe approach for OLTs treatment. Cellular parameters seem to influence the treatment outcomes, thus further attention should be given to the intraoperatively applied products. Level of evidence Level IV.

Theoretical simulations of dispersed solid particle behaviour inside a scrubbing pool within the bubble rise region are presented. The goal is to evaluate the decontamination factor of the particles during the pool scrubbing process. The basic phenomena of pool scrubbing are described. The setup used for the simulation validation is presented. Then, the boundary and initial conditions of the PECA experiments, which were performed at CIEMAT (Madrid, Spain) and were used for simulations, are presented. The subgrid model for decontamination through transfer of particles from gas bubbles to the surrounding liquid is described. The calculation results are evaluated and compared with the part of the PECA experimental results to which the proposed modelling is applicable.

Background and Objectives: The subcutaneous (SC) formulation of vedolizumab has proven to be effective for the maintenance of remission after intravenous induction. Little is known about the efficacy of switching from intravenous maintenance treatment to SC. We aimed to assess the real-world efficacy of switching to SC treatment and to assess the impact of a baseline treatment regimen. Materials and Methods: In this observational cohort study, adult patients with inflammatory bowel disease who were switched to SC vedolizumab maintenance treatment were enrolled. Patients after intravenous induction and patients who switched from intravenous maintenance treatment (every 8 weeks or every 4 weeks) were included. The SC vedolizumab dosing was 108 mg every 2 weeks, regardless of the previous regimen. The clinical, biochemical, and endoscopic disease activity parameters and vedolizumab serum concentrations at the time of the switch and at the follow-up were assessed. Results: In total, 135 patients (38% Crohn’s disease, 62% ulcerative colitis) were switched to SC vedolizumab treatment. The median time to the first follow-up (FU) was 14.5 weeks (IQR 12–26), and the median time to the second FU was 40 weeks (IQR 36–52). Nine patients (7%) discontinued SC vedolizumab treatment, with two-thirds of them discontinuing due to active disease. In all dosing regimens, there were no significant changes in the clinical scores and CRP at the baseline and first and second FUs. Clinical and biochemical remission appeared to be maintained irrespective of the previous dosing regimen. Conclusions: The results of this real-world study suggest that the maintenance of clinical and biomarker remission can be achieved in patients who switched from intravenous to SC vedolizumab. The baseline vedolizumab dosing regimen (every 4 weeks versus every 8 weeks) did not have an impact on outcomes.

The Black Notebooks [Schwarze Hefte] are personal notebooks that Heidegger wrote from the beginning of the 1930s to the end of the war. The first notebook has been lost, but transcripts of the next fourteen, which originated in the decade 1931–1941, were published in 2014 in three consecutive volumes of the philosopher’s Gesamtausgabe (more recently, further notebooks up to 1970 have been published). Their publication triggered a new wave of public polemics about his Nazism and anti-Semitism. This paper evaluates Heidegger’s multistage and multilayered relationship to Judaism and National Socialism, and the most prominent modern interpretations of that relationship, especially in light of the Black Notebooks. Among such readings, some of the most profound and lucid are those of the editor of the German edition of the Notebooks, Peter Trawny, and the Spanish philosopher Jesus Adrian Escudero. Many early reactions to the first publication of the notebooks were characterized by a combative outrage that was not supported by serious study and understanding of the material in question. This paper studies the reasons why that initial, sensationalist reaction stimulated precisely the opposite effect from what might be expected: Instead of jeopardizing Heidegger’s well-established place in the Western philosophical canon, the controversies of 2014 triggered a kind of renaissance of interest in his life and work.

This paper deals with the more than century-long history of staging Sophocles’s Antigone on Slovenian professional stages. After the first, awkward attempt by Hinko Nučič in the Drama Ljubljana (1912), the impression was saved by the very well received second production directed by Fran Lipah (1939). The reception of Antigone in the wider Yugoslavia in the first decade after the war was marked by a highly successful production in Belgrade (1950), directed by Tomislav Tanhofer and Miroslav Belović. Also, the key to the further development of the (ambivalent) Slovenian relationship with the myth of Antigone – in its dramatic and theatrical as well as its philosophical reception – was the literary adoption of the myth among Slovenian emigrés to Argentina dealing with the trauma of the post-war massacres. The third Slovenian production, and the first post-war one, directed by Herbert Grün at the Celje City Theatre (1956), was carefully thought out in dramaturgic and aesthetic terms. However, the result on the stage left critics with mixed impressions. Then followed the rise and supremacy of Dominik Smole’s Antigone (1960). With a little help from its “peers,” the other contemporary Antigones, it managed in an intriguing way to oust Sophocles’s tragedy of the same name from Slovenian professional stages for half a century, with one important exception: until 2013, the Celje City Theatre remained the only theatre to stage it in the post-war period. It was staged for the second time in 1973 with the production by Franci Križaj, which got middling reviews – Križaj, incidentally, also directed the first and fifth stagings of Smole’s Antigone – and for the third time in 2011, in the critically well-received interpretation of the Serbian director Anđelka Nikolić, which was characterised by its aesthetically anachronistic and genre-fluid approach to the original.

Sofoklejeva Antigona ima bogato in edinstveno, več kot stoletno zgodovino uprizarjanja na slovenskih poklicnih odrih. Začela se je z neuspelo predstavo pod taktirko Hinka Nučiča na odru ljubljanske Drame leta 1912 in nadaljevala s priljubljeno postavitvijo Frana Lipaha v istem gledališču na predvečer druge svetovne vojne. Po vojni je primat pri uprizarjanju te tragedije prevzelo Slovensko ljudsko gledališče Celje (tedaj se je imenovalo Mestno gledališče Celje); vse do leta 2013 je bilo celo edino slovensko poklicno gledališče, ki jo je uprizarjalo, prvič leta 1956 (r. Herbert Grün), nato še leta 1973 (r. Franci Križaj), nazadnje pa leta 2011 (r. Anđelka Nikolić). Glavni razlog za to nenavadno odsotnost Sofoklejeve Antigone na drugih slovenskih poklicnih odrih je bila najverjetneje izjemna priljubljenost Smoletove drame z istim naslovom, ki je bila v tem času uprizorjena kar osemkrat, še dodatno pa so Sofokleja izrivale tudi (redkejše) uprizoritve drugih modernih Antigon (Dušan Jovanović, Miro Gavran, Janusz Głowacki). Zadnje desetletje je vendarle prineslo preporod zanimanja za Sofoklejevo različico (in obenem tudi zaton zanimanja za uprizarjanje Smoleta, kar pritrjuje naši spekulaciji o njunem programskem konkuriranju). Po kritiško dobro sprejeti celjski uprizoritvi v režiji Anđelke Nikolić, sta bili leta 2013 prvič na sporedu dve uprizoritvi, prva v Mestnem gledališču ljubljanskem (bralna uprizoritev, r. Ira Ratej) in druga v Lutkovnem gledališču Ljubljana (r. Marko Čeh). Nazadnje, leta 2017, pa se je Antigona v udarnem slogu končno vrnila tudi v ljubljansko Dramo (r. Eduard Miler). Članek pregledno obravnava vse naštete uprizoritve in jih ovrednoti s pomočjo sočasne kritiške ter poznejše gledališkozgodovinske recepcije.

Martin Heidegger je svoje branje Sofoklove Antigone razgrnil v dveh znamenitih sklopih predavanj na Univerzi v Freiburgu; prvi sklop, ki ga je študentom predstavil leta 1935, je osemnajst let pozneje s popravki in dopolnitvami objavil v knjigi Uvod v metafiziko (Einführung in die Metaphysik); drugega, ki ga je naslovil Hölderlinova himna »Ister« (Hölderlins Hymne »Der Ister«), je lahko leta 1942, sredi vojne vihre, podal le v okrnjeni različici, v natisnjeni celoti pa je svetovni javnosti postal dostopen šele leta 1984. Članek preučuje razloge, zakaj je razkritje Heideggerjeve druge obravnave Antigone – ki s prvo vzpostavlja intriganten interpretativni kontrast – odigralo ključno vlogo v osrednjem filozofskem projektu Tineta Hribarja in s tem v širši slovenski recepciji mita o Antigoni od druge polovice osemdesetih let do danes.

Research Question (RQ): What is the role of organisational commitment in health, especially in the context of other work-related psychosocial factors (optimism, empowerment, stressful working conditions, job insecurity, and satisfactory payment). Purpose: The aim of the paper is to examine the role of organisational commitment in employee’s health. Method: An ISSP survey on a subsample of 589 workers in Slovenia was statistically analysed, using 1) a bivariate Pearson correlation test;2) a hierarchical multivariate linear regression to compare two models, where to see the role of organisational commitment, health was predicted by work-related psychosocial factors in a model with and in a model without organisational commitment, and 3) structural equation modelling to understand interrelations amongst analysed concepts. Results The results shows all analysed factors contribute to health, but not all directly. Health was found to be directly related to stressful working conditions, optimism, and affective organisational commitment. The latter was found to mediate the effects of stressful working conditions, satisfactory payment and optimism on health. Organisation: The results have a significant impact on a more detailed review of the factors that contribute to better working conditions for healthier employees When employees are committed, they not only stay in the organisation, but they are also healthier and consequently perform better, thus benefits could be seen for employers and employees. It is useful for managers to have knowledge of psychological empowerment, job satisfaction, and organizational commitment, as they can utilize these elements to motivate, develop, and manage employees. Society: As working population is the one that represent the main active population in society, it is important to generate working conditions for healthier workforce. Understanding the role of organisational commitment, and other work-related psychosocial factors for health could benefit not only for organisations and employees, but for other society members, that rely on working population, as well. Originality: The study statistically examines the conceptual research model, where it does not stop on bivariate correlations, or model with one dependent variable, as found in many other studies, but explore inner correlations among factors, thus provide more detailed insight to the relations among organisational commitment, employee’s health and work-related psychosocial factors (optimism, empowerment, stressful working conditions, job insecurity, and satisfactory payment). With our findings we contribute to the discussion on a constructive and future oriented approach to provide working conditions that would lead to committed and healthier workforce. We suggest that policy makers and human resource managers in organisations create working conditions that are focused on improving health. By doing so, affective organisational commitment should be one of the top priorities. Limitations/further research: The study was cross-sectional. Our sample was limited to employees in Slovenia. Our study was limited by the scope of secondary data available; health predictors were selected in accordance with theory and available indicators in the existing survey; limited to main factors: health, organisational commitment and work-related psychosocial factors (optimism, empowerment, stressful working conditions, job insecurity, and satisfactory payment). Future research could focus also on other health related factors (such as genetics, certain lifestyles, the environment, and susceptibility to diseases), include longitudinal approach and compare different geographical contexts.

The authors present and discuss the results of a nation-wide survey on food safety knowledge among professional food handlers in Slovenia. The data were collected via a telephone survey using a well-established questionnaire adapted to the Slovenian context. Altogether, 601 respondents from hotels, restaurants, catering, and confectionery units completed the questionnaire. To assess food safety knowledge among food handlers in both general and specific domains, three indexes (a General Knowledge Index, a Personal Knowledge Index, and a Temperature Knowledge Index) were created. Among them, the Temperature Knowledge Index revealed the largest gaps in knowledge. An insufficient transfer of food safety knowledge from managers and chefs to assistant chefs and kitchen assistants in establishments where more persons handle food was evident, while a course titled “Hygiene Minimum” of standardised training from the past still significantly contributes to food safety knowledge. The results suggest a need for improvement in the current system of food safety training courses for professional food handlers in Slovenia. The human factor in the food supply chain still has a significant role in ensuring food safety culture, and therefore must become a more important part of the food safety management system.

Background and Objectives: The main drawback of lipofilling is fat transplant volume loss, which makes long-term results unreliable. This study’s aim was to assess the influence of an adipose-derived stromal vascular fraction (SVF) on volume retention in large-volume fat grafts. Materials and Methods: A murine model was used for the in vivo evaluation of fat-graft volume changes over 6 months. We used 28 immunocompromised nude NU(NCr)-Foxn1nu mice and human fat tissue as a liposuction by-product. Part of the fat tissue was used for SVF preparation. We created a fat transplant without SVF (SVF-) and with SVF (SVF+) groups. Large-volume grafts were injected above the sacrum and scapula in the same animal. Volume loss was evaluated using three-dimensional optical scanning at 14 days (T1), 3 months (T2), and 6 months (T3) after transplantation. Scans were processed with Artec Studio software to obtain stereolithography files. The volumes were calculated in RapidForm software 2006. Results: The highest volume loss was observed above the scapula at T3 (SVF- 85%; SVF+ 75%). There was a significant difference in volume between SVF-/SVF+ for grafts above the sacrum at T2, with lower loss in SVF+, and the significance became stronger at T3. The difference in volume loss was also significant above the scapula between SVF-/SVF+ at T3. Conclusions: Although we found a beneficial effect of SVF on the long-term survival of large-volume fat tissue transplants, volume loss due to other contributing factors was high.

Recommendations for the dental treatment of patients with head and neck cancer (HNC) in Slovenia treated with radiation follow the recommendations and guidelines of the Royal College of Surgeons of England created in association with the British Society for Disability and Oral Health, the Recommendations for the treatment of patients with head and neck cancer in Slovenia and at the same time consider the existing capabilities of the Slovenian health care system. The recommendations aim to prevent or reduce complications in the oral cavity due to radiation therapy. They define the dental care before, during and after radiation therapy at all three levels of dental care, which ensures the timeliness and accessibility of dental care. The recommendations represent a unified opinion of all stakeholders in the field of dental treatment of HNC patients in the country.

Povezava med mitom o Antigoni in slovenskimi povojnimi izvensodnimi poboji, ki jo je odmevno opredelil Tine Hribar v filozofskih in političnih spisih iz druge polovice osemdesetih let, se v kontekstu slovenske literarne zgodovine in komparativistike najpogosteje pojavlja v interpretacijah Antigone Dominika Smoleta. Pričujoči članek, ki zasleduje stoletno slovensko recepcijo antigonskega mita med letoma 1875 in 1974 – od njegove prve pojavitve v slovenskem jeziku do prve eksplicitne upodobitve slovenskih konfliktov iz časa 2. svetovne vojne skozi njegovo prizmo –, pokaže, da je literarna povezava med tem mitom in osrednjo zgodovinsko travmo tega prostora bistveno širša od Smoletove slovite drame.

Background: The trend toward disposable products in gastrointestinal endoscopy, including single-use endoscopes, remains undeterred, even though crucial questions of sustainability and performance have not been sufficiently studied. The first single-use therapeutic gastroscope was recently approved in Europe, but clinical data to support its use are currently lacking. We aimed to evaluate the performance of this novel device in routine procedures requiring a large working channel., Methods: Between January and May 2024, consecutive patients with an indication for therapeutic gastroscopy were included prospectively. The primary outcome was intraprocedural technical success rate., Results: Eight gastrointestinal bleedings, two pancreatic necrosectomies, four foreign body removals, four stent placements, and two cryo-balloon ablations were performed. The technical success rate was 84% (16/19 patients). Crossover to a standard endoscope was required in three procedures. Clinical success was achieved in all cases with technical success. Overall user experience was 3.2 on a Likert scale of 1-5. No adverse events were reported., Conclusions: The single-use therapeutic gastroscope demonstrated feasibility in various therapeutic procedures; however, a 16% crossover rate and fair user assessment score suggest that further technical improvements to the device are necessary., Competing Interests: The single-use therapeutic gastroscopes used in this study were funded by Ambu GmbH. The study design, execution, and manuscript preparation were carried out without any influence from the company. C. Römmele reports consultancy fees from Ambu Innovations and Ambu GmbH, and unpaid consultancy for Boston Scientific. H. Messmann reports relationships with Ambu, Boston Scientific, Fujifilm, Hitachi, and Olympus. He has also received honoraria from Olympus and consultancy fees from Ambu, Boston Scientific, and Olympus. A. Ebigbo reports consultancy fees from Ambu and Olympus. M. Ayoub, J. Wanzl, V. Tadic, G. Braun, T. Weber, M.W. Scheppach, D. Roser, K. Matic, and S. Nagl declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies., Objective: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring., Methods: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022., Results: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted., Conclusion: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted., (© 2024. Crown.)

Proliferation of COVID-19 research underscored the need for improved awareness among investigators, research staff and bedside clinicians of the operational details of clinical studies. The objective was to describe the genesis, goals, participation, procedures, and outcomes of two research operations committees in an academic ICU during the COVID-19 pandemic., Design: Two-phase, single-center multistudy cohort., Setting: University-affiliated ICU in Hamilton, ON, Canada., Patients: Adult patients in the ICU, medical stepdown unit, or COVID-19 ward., Interventions: None., Measurements and Main Results: An interprofessional COVID Collaborative was convened at the pandemic onset within our department, to proactively coordinate studies, help navigate multiple authentic consent encounters by different research staff, and determine which studies would be suitable for coenrollment. From March 2020 to May 2021, five non-COVID trials continued, two were paused then restarted, and five were launched. Over 15 months, 161 patients were involved in 215 trial enrollments, 110 (51.1%) of which were into a COVID treatment trial. The overall informed consent rate (proportion agreed of those eligible and approached including a priori and deferred consent models) was 83% (215/259). The informed consent rate was lower for COVID-19 trials (110/142, 77.5%) than other trials (105/117, 89.7%; p = 0.01). Patients with COVID-19 were significantly more likely to be coenrolled in two or more studies (29/77, 37.7%) compared with other patients (13/84, 15.5%; p = 0.002). Review items for each new study were collated, refined, and evolved into a modifiable checklist template to set up each study for success. The COVID Collaborative expanded to a more formal Department of Critical Care Research Operations Committee in June 2021, supporting sustainable research operations during and beyond the pandemic., Conclusions: Structured coordination and increased communication about research operations among diverse research stakeholders cultivated a sense of shared purpose and enhanced the integrity of clinical research operations., Competing Interests: Dr Cook holds a Canada Research Chair from the Canadian Institutes for Health Research. Dr. Lewis holds the Constantine Douketis New Researcher Award from the Research Institute of St. Joseph’s Healthcare Hamilton. Dr. Kho holds a Canada Research Chair from the Canadian Institutes for Health Research. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)