Clonal background and routes of plasmid transmission underlie antimicrobial resistance features of bloodstream Klebsiella pneumoniae.

Bloodstream infections caused by the opportunistic pathogen Klebsiella pneumoniae are associated with adverse health complications and high mortality rates. Antimicrobial resistance (AMR) limits available treatment options, thus exacerbating its public health and clinical burden. Here, we aim to elucidate the population structure of K. pneumoniae in bloodstream infections from a single medical center and the drivers that facilitate the dissemination of AMR. Analysis of 136 short-read genome sequences complemented with 12 long-read sequences shows the population consisting of 94 sequence types (STs) and 99 clonal groups, including globally distributed multidrug resistant and hypervirulent clones. In vitro antimicrobial susceptibility testing and in silico identification of AMR determinants reveal high concordance (90.44-100%) for aminoglycosides, beta-lactams, carbapenems, cephalosporins, quinolones, and sulfonamides. IncF plasmids mediate the clonal (within the same lineage) and horizontal (between lineages) transmission of the extended-spectrum beta-lactamase gene blaCTX-M-15. Nearly identical plasmids are recovered from isolates over a span of two years indicating long-term persistence. The genetic determinants for hypervirulence are carried on plasmids exhibiting genomic rearrangement, loss, and/or truncation. Our findings highlight the importance of considering both the genetic background of host strains and the routes of plasmid transmission in understanding the spread of AMR in bloodstream infections.

Revision after prior failed pectus excavatum repair: higher risks and greater complications than primary surgery.

Background: Revision of a prior failed pectus excavatum (PE) repair is occasionally required. These procedures may be technically more complex and have a greater risk of complications. This study was performed to evaluate the outcomes of adult patients undergoing revision procedures. Methods: A retrospective review of adult patients who underwent revision of a prior PE repair from 2010 to 2023 at Mayo Clinic Arizona was performed. Patients were classified by prior procedure [minimally invasive repair of pectus excavatum (MIRPE), Open/Ravitch, and both] and the type of revision procedure performed [MIRPE, hybrid MIRPE, complex hybrid reconstruction, or complex reconstruction of acquired thoracic dystrophy (ATD)]. Outcomes and complications of these groups were analyzed and compared. Results: In total, 190 revision cases were included (mean age was 33±10 years; 72.6% males, mean Haller Index: 4.4±1.8). For the initial repair procedure, 90 (47.4%) patients had a previous MIRPE, 87 (45.8%) patients a prior open repair, and thirteen (6.8%) patients had both. Furthermore, 30 (15.8%) patients had two or more prior interventions. Patients having had a prior MIRPE were able to be repaired with a revision MIRPE in 82.2% of the cases. Conversely, patients with a prior open repair (including those who had both prior MIRPE and open repairs) were much more likely to require complex reconstructions (85%) as none of the ATD patients in this group had an attempted MIRPE. Operative times were shortest in the MIRPE redo approach and longest in the complex reconstruction of the ATD patients (MIRPE 3.5±1.3 hours, ATD 6.9±1.8 hours; P<0.001). The median length of hospital stay was 5 days [interquartile range (IQR), 3.0 days] with the shortest being the MIRPE approach and the longest occurring in the complex reconstruction of the ATD patients [MIRPE 4 days (IQR, 3.0 days); ATD 7 days (IQR, 4.0 days); P<0.001]. Major and minor complications were more frequent in the ATD complex reconstruction group. Preoperative chronic pain was present in over half of the patients (52.6%). Although resolution was seen in a significant number of patients, significant pain issues persisted in 8.8% of the patients postoperatively. Overall, persistent, long term chronic pain was greatest in the post open/Ravitch patient group (open 13.6% vs. MIRPE 3.6%, P=0.02). Conclusions: Revision of a prior failed PE repair can be technically complex with a high risk of complications, prolonged duration of surgery, and lengthy hospitalization. Chronic pain is prevalent and its failure to completely resolve after surgery is not uncommon. The initial failed repair will influence the type of procedure that can be performed and potentially subsequent complications. Even when some recurrences after previous PE surgeries can be repaired with acceptable results, this study demonstrates the importance of proper primary repair due to these increased risks.

Local photo-crosslinking of native tissue matrix regulates cell function.

Within most tissues, the extracellular microenvironment provides mechanical cues that guide cell fate and function. Changes in the extracellular matrix such as aberrant deposition, densification and increased crosslinking are hallmarks of late-stage fibrotic diseases that often lead to organ dysfunction. Biomaterials have been widely used to mimic the mechanical properties of the fibrotic matrix and study cell function. However, the initiation of fibrosis has largely been overlooked, due to the challenges in recapitulating early fibrotic lesions within the native extracellular microenvironment. Using visible light mediated photochemistry, we induced local crosslinking and stiffening of extracellular matrix proteins within ex vivo murine and human tissue. In ex vivo lung tissue of epithelial cell lineage-traced mice, local matrix crosslinking mimicked early fibrotic lesions that increased alveolar epithelial cell spreading, differentiation and extracellular matrix remodeling. However, inhibition of cytoskeletal tension or integrin engagement reduced epithelial cell spreading and differentiation, resulting in alveolar epithelial cell dedifferentiation and reduced extracellular matrix deposition. Our findings emphasize the role of local extracellular matrix crosslinking and remodeling in early-stage tissue fibrosis and have implications for ex vivo disease modeling and applications to other tissues.

Incidence and survival of multiply revised knee arthroplasties in Denmark 1998-2021: a nationwide register-based study.

PURPOSE: The primary aim of our study was to identify the absolute incidence and implant survival of multiply revised knee arthroplasties based on nationwide register data. The secondary aim was to determine the change in the absolute incidence and implant survival of multiply revised knee arthroplasties Methods: We performed a retrospective observational study of primary knee arthroplasties using several nationwide Danish registers. All primary knee arthroplasties performed in Denmark from 1998 to 2021 were identified. From these primary arthroplasties, revision procedures were identified. Kaplan-Meier plots were used in survival analysis to estimate the likelihood of implant survival. RESULTS: 161,384 primary knee arthroplasties and their revisions performed between 1998 and 2021 were identified; of 13,786 (8.5%) revisions there were 10,638 1st revisions, 2,148 2nd revisions, 624 3rd revisions, 223 4th revisions, and 153 procedures that had been revised more than 4 times. The 10-year revision-free survival of primary arthroplasties was 92.3% (95% confidence interval [CI] 92.2-92.5). First-time revisions had a 10-year revision-free survival of 75.9% (CI 74.9-76.9). The 10-year survival of second- and third-time revisions was 65.1% (CI 62.6-67.6) and 57.8% (CI 53.4-62.5), respectively. The 10-year implant survival probabilities of primary knee arthroplasties were 91.4% in 1998-2009 and 93.3% in 2010-2021 (difference 2.2%). The 10-year implant survival probabilities of 1st revisions were 77% in 1998-2009 and 75% in 2010-2021 (difference -2.4%). CONCLUSION: We found that 0.3% of all primary knee arthroplasties resulted in 3 or more revisions. The implant survival decreased for each consecutive revision, with almost half of the 3rd revisions being re-revised within 10 years. The 10-survival of the primary implant was higher in 2010-2021, and the 10-year survival of the 1st revision was higher in 1998-2009.

Neolithic Yersinia pestis infections in humans and a dog.

Yersinia pestis has been infecting humans since the Late Neolithic (LN). Whether those early infections were isolated zoonoses or initiators of a pandemic remains unclear. We report Y. pestis infections in two individuals (of 133) from the LN necropolis at Warburg (Germany, 5300-4900 cal BP). Our analyses show that the two genomes belong to distinct strains and reflect independent infection events. All LN genomes known today (n = 4) are basal in the phylogeny and represent separate lineages that probably originated in different animal hosts. In the LN, an opening of the landscape resulted in the introduction of new rodent species, which may have acted as Y. pestis reservoirs. Coincidentally, the number of dogs increased, possibly leading to Y. pestis infections in canines. Indeed, we detect Y. pestis in an LN dog. Collectively, our data suggest that Y. pestis frequently entered human settlements at the time without causing significant outbreaks.

The Experience of the Virtual Interview Process for Hand Fellowship Program Directors.

Purpose: Due to the Coronavirus Disease-19 pandemic, the fellowship application process has transitioned from in-person interviews to virtual interviews. Although several studies have assessed the impact of Coronavirus Disease-19 on residency and fellowship interviews, fewer studies have investigated the program director's perspective. Therefore, the aim of this study was to assess the experience of virtual interviews on hand fellowship program directors and understand some of the important factors that may make an applicant more competitive. Methods: A 21-question survey was conducted through Google Forms and distributed through a standardized email to hand fellowship program directors and coordinators. Questions used a 5-point Likert scale with the opportunity for respondents to answer some questions in a free-response format. Statistical analysis was conducted with significance assigned to P values < .05. Results: Ninety-three surveys were distributed, of which 35 responses were obtained, corresponding to a 37.6% survey response rate. Program directors reported that they tended to place more emphasis on applicant's curriculum vitae, calls from colleagues, and applicants that they had previously met. In addition, program directors felt that applicants were able to accurately represent themselves through the virtual format. Finally, most program directors stated that they were highly likely to continue to offer virtual interviews. Conclusions: With several parenting organizations and program directors affirming that they are comfortable with proceeding with virtual interviews, it is essential for hand fellowship applicants to understand what factors program directors may perceive as more important. It is possible that the virtual interview process may effectively achieve suitable matches between applicants and institutions. Type of study/level of evidence: Decision analysis IIIb.

Repair of genomic interstrand crosslinks.

Genomic interstrand crosslinks (ICLs) are formed by reactive species generated during normal cellular metabolism, produced by the microbiome, and employed in cancer chemotherapy. While there are multiple options for replication dependent and independent ICL repair, the crucial step for each is unhooking one DNA strand from the other. Much of our insight into mechanisms of unhooking comes from powerful model systems based on plasmids with defined ICLs introduced into cells or cell free extracts. Here we describe the properties of exogenous and endogenous ICL forming compounds and provide an historical perspective on early work on ICL repair. We discuss the modes of unhooking elucidated in the model systems, the concordance or lack thereof in drug resistant tumors, and the evolving view of DNA adducts, including ICLs, formed by metabolic aldehydes.

WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation.

One of the key events in autophagy is the formation of a double-membrane phagophore, and many regulatory mechanisms underpinning this remain under investigation. WIPI2b is among the first proteins to be recruited to the phagophore and is essential for stimulating autophagy flux by recruiting the ATG12-ATG5-ATG16L1 complex, driving LC3 and GABARAP lipidation. Here, we set out to investigate how WIPI2b function is regulated by phosphorylation. We studied two phosphorylation sites on WIPI2b, S68 and S284. Phosphorylation at these sites plays distinct roles, regulating WIPI2b's association with ATG16L1 and the phagophore, respectively. We confirm WIPI2b is a novel ULK1 substrate, validated by the detection of endogenous phosphorylation at S284. Notably, S284 is situated within an 18-amino acid stretch, which, when in contact with liposomes, forms an amphipathic helix. Phosphorylation at S284 disrupts the formation of the amphipathic helix, hindering the association of WIPI2b with membranes and autophagosome formation. Understanding these intricacies in the regulatory mechanisms governing WIPI2b's association with its interacting partners and membranes, holds the potential to shed light on these complex processes, integral to phagophore biogenesis.

Machine-learned molecular mechanics force fields from large-scale quantum chemical data.

The development of reliable and extensible molecular mechanics (MM) force fields-fast, empirical models characterizing the potential energy surface of molecular systems-is indispensable for biomolecular simulation and computer-aided drug design. Here, we introduce a generalized and extensible machine-learned MM force field, espaloma-0.3, and an end-to-end differentiable framework using graph neural networks to overcome the limitations of traditional rule-based methods. Trained in a single GPU-day to fit a large and diverse quantum chemical dataset of over 1.1 M energy and force calculations, espaloma-0.3 reproduces quantum chemical energetic properties of chemical domains highly relevant to drug discovery, including small molecules, peptides, and nucleic acids. Moreover, this force field maintains the quantum chemical energy-minimized geometries of small molecules and preserves the condensed phase properties of peptides and folded proteins, self-consistently parametrizing proteins and ligands to produce stable simulations leading to highly accurate predictions of binding free energies. This methodology demonstrates significant promise as a path forward for systematically building more accurate force fields that are easily extensible to new chemical domains of interest.

A Database Tool Integrating Genomic and Pharmacologic Data from Adrenocortical Carcinoma (ACC) Cell Lines, PDX, and Patient Samples.

Adrenocortical carcinoma (ACC) is a rare and highly heterogeneous disease with a notably poor prognosis due to significant challenges in diagnosis and treatment. Emphasising on the importance of precision medicine, there is an increasing need for comprehensive genomic resources alongside well-developed experimental models to devise personalized therapeutic strategies. We present ACC_CellMinerCDB, a substantive genomic and drug sensitivity database (available at https://discover.nci.nih.gov/acc_cellminercdb) comprising ACC cell lines, patient-derived xenografts, surgical samples, combined with responses to over 2,400 drugs examined by NCI and NCATS. This database exposes shared genomic pathways among ACC cell lines and surgical samples, thus authenticating the cell lines as research models. It also allows exploration of pertinent treatment markers such as MDR-1, SOAT1, MGMT, MMR and SLFN11, and introduces the potential to repurpose agents like temozolomide for ACC therapy. ACC_CellMinerCDB provides the foundation for exploring larger preclinical ACC models.

Transcirculation Approaches to Endovascular Flow Diversion of Intracranial Aneurysms: A Systematic Review With Technical Considerations.

BACKGROUND AND OBJECTIVES: Flow diversion (FD) of intracranial aneurysms (IAs) is an increasingly used and efficacious treatment modality. Transcirculation approaches, or approaches that cross the contralateral or anteroposterior arterial supply before reaching a target vessel, have been used to treat cerebrovascular pathologies when traditional approaches are unsuitable or require intraoperative complication management. This study sought to review IAs treated with FD using a transcirculation approach to determine the technique's safety and efficacy. METHODS: A systematic review of the PubMed, Scopus, Web of Science, and Embase databases was completed per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included if they described transcirculation approaches in adult patients with IAs undergoing FD. Outcomes of interest included intraoperative complications and aneurysm occlusion rates. RESULTS: Twelve studies with 19 patients (N = 19, mean age = 54.1 y, 89.5% female) were identified. Wide-necked (N = 5, 26.3%) and saccular (N = 5, 26.3%) aneurysms were most represented, while 57.9% (N = 11) of aneurysms were unruptured and 15.8% (N = 3) of aneurysms were ruptured. The mean aneurysm sac and neck size were 16.9 mm and 11.9 mm, respectively. The most commonly deployed flow diverter was the Pipeline Embolization Device (N = 14, 73.9%). Successful FD (complete occlusion and/or good wall apposition) was recorded in 84.6% of qualifying patients with follow-up data, while 2 patients (15.4%) developed an intraoperative carotid-cavernous fistula. CONCLUSION: Transcirculation approaches to FD offer neurointerventionalists a safe and efficacious method for device deployment, rescue scenarios, and challenging anatomy. Prospective studies may determine the most appropriate indications for transcirculation approaches to FD, while novel, lower profile devices may improve its technical feasibility and safety.

Lack of Evidence for Vaccine-Associated Enhanced Disease From COVID-19 Vaccines Among Adults in the Vaccine Safety Datalink.

PURPOSE: Vaccine-associated enhanced disease (VAED) is a theoretical concern with new vaccines, although trials of authorized vaccines against SARS-CoV-2 have not identified markers for VAED. The purpose of this study was to detect any signals for VAED among adults vaccinated against coronavirus disease 2019 (COVID-19). METHODS: In this cross-sectional study, we assessed COVID-19 severity as a proxy for VAED among 400 adults hospitalized for COVID-19 from March through October 2021 at eight US healthcare systems. Primary outcomes were admission to an intensive care unit (ICU) and severe illness (score ≥6 on the World Health Organization [WHO] Clinical Progression Scale). We compared the risk of outcomes among those who had completed a COVID-19 vaccine primary series versus those who were unvaccinated. We incorporated inverse propensity weights for vaccination status in a doubly robust regression model to estimate the causal average treatment effect. RESULTS: The causal risk ratio in vaccinated versus unvaccinated was 0.36 (95% confidence interval [CI], 0.15-0.94) for ICU admission and 0.46 (95% CI, 0.25-0.76) for severe illness. CONCLUSION: Among hospitalized patients, reduced disease severity in those vaccinated against COVID-19 supports the absence of VAED.

Automated task-level autonomy assessment in robotic surgery.

INTRODUCTION: Surgical autonomy for trainees has remained elusive to quantify. Proportion of active control time (ACT) of a trainee during a robotic case can be used as a broad measure of autonomy. However, this metric lacks in the granular detail of quantifying at what specific steps trainees were actively participating. We aim to quantify trainee involvement during robotic-assisted hiatal hernia repair at a task-specific level. METHODS: We performed a retrospective review of surgical performance data from robotic-assisted hiatal hernia repairs performed. These cases were segmented into 5 tasks by AI-assisted annotation with human review. The segmented tasks included: hiatal dissection, gastric fundus mobilization, mediastinal dissection, cruroplasty and fundoplication. Tasks were excluded if video segmentation of tasks was incorrect. During each task, ACT was recorded for resident, fellow and attending. Resident and fellow ACT per task was compared using the Mann-Whitney U test. RESULTS: Residents had the highest %ACT in the hiatal dissection (53%), gastric fundus mobilization (84%) and fundoplication (57%) tasks. Fellows had greater than 80% ACT in all 5 tasks, with the highest %ACT in the gastric fundus mobilization (100%) and hiatal dissection (88%). There was a significant difference between resident and fellow ACT during mediastinal dissection and cruroplasty. CONCLUSIONS: This study demonstrates how objective performance metrics and automated case segmentation can quantify trainee participation at a task-specific level. By utilizing data afforded by a robotic surgery platform, we are able to provide an objective and automated form of assessment with minimal impact on the workflow of attendings and residents. Our findings can serve to inform residents on what steps they can expect to be involved in during the procedure, appropriate to their PGY level. With this task-level data, we can provide a roadmap for trainee progression to achieve full surgical autonomy.

Preventive Antibiotic Use and Complications After Endoscopic Retrograde Cholangiopancreatography in Patients Hospitalized for Primary Sclerosing Cholangitis.

BACKGROUND: The American Society for Gastrointestinal Endoscopy recommends prophylactic antibiotics before endoscopic retrograde cholangiopancreatography (ERCP) in primary sclerosing cholangitis (PSC). We assessed the impact of this approach on the incidence of post-ERCP outcomes using nationwide data. METHODS: Using 2015-2021 Nationwide Inpatient Sample data and relevant ICD-10 codes, we analyzed adult hospitalizations for PSC who underwent ERCP, with and without antibiotic prophylaxis. Hierarchical multivariate logistic regression analysis was used to assess the association between prophylactic antibiotic use and post-ERCP complications including sepsis, acute cholangitis, and acute pancreatitis. RESULTS: We analyzed 32,972 hospitalizations for PSC involving ERCP, with 12,891 admissions (39.1%) receiving antibiotics before ERCP (cases) and 20,081 (60.9%) serving as controls. Cases were older than controls (mean age: 64.2 ± 8.6 vs. 61.3 ± 6.1 years; P = 0.020). Compared with controls, hospitalizations with antibiotic prophylaxis had a higher male population (7,541 (58.5%) vs. 11,265 (56.1%); P < 0.001) and higher comorbidity burden (Charlson comorbidity index score of ≥2: 5,867 (45.5%) of cases vs. 8,996 (44.8%) of controls; P = 0.01). Incidence of post-ERCP septicemia was 19.1% (6,275) with 2,935 incidences (22.8%) among cases compared with 3,340 (16.6%) among controls. Antibiotic prophylaxis did not significantly improve the odds of septicemia (aOR: 0.85; 95% CI: 0.77 - 1.09; P = 0.179). Approximately 2,271 (6.9%) cases of acute cholangitis and 5,625 (17.1%) cases of acute post-ERCP pancreatitis were recorded. After adjustments for multiple variables, no significant difference was observed in the odds of cholangitis (aOR: 0.87; 95% CI: 0.98 - 1.45; P = 0.08). However, antibiotic prophylaxis was correlated with a statistically significant reduction in the odds ratio of acute post-ERCP pancreatitis (aOR: 0.61; 95% CI: 0.57 - 0.66; P < 0.001). CONCLUSION: The use of antibiotic prophylaxis in hospitalizations with PSC was correlated with a significant reduction in the odds of post-ERCP pancreatitis. Antibiotic prophylaxis did not improve the odds of post-ERCP sepsis or cholangitis. Prophylactic use of antibiotics should be individualized, considering both their anti-infective benefits and potential impact on the biochemical markers of liver disease.

High parathyroid hormone rather than low vitamin D is associated with reduced event-free survival in childhood cancer.

BACKGROUND: Vitamin D deficiency is linked to poor cancer outcomes, but the impact of its consequence, elevated parathyroid hormone (PTH) remains understudied. PTH receptor activation influences cancer progression in vitro, yet the effect of elevated PTH on pediatric cancer survival is unexamined. METHODS: This retrospective study examines associations between PTH, 25-OH vitamin D (25OHD), and event-free survival (EFS) and overall survival (OS) in pediatric cancer patients. Laboratory data from 4,349 patients (0-18 years) at a tertiary pediatric cancer unit were analyzed for the highest PTH and lowest 25OHD levels at diagnosis and the following five years. Data on relapse, secondary malignancies, and mortality were stratified by PTH levels above/below the cohort median (47 pg/ml) and 25OHD levels ≤ 30 nmol/L. EFS and OS were analyzed, and hazard ratios (HR) were calculated for the entire cohort and six cancer subgroups. RESULTS: PTH and 25OHD values were available for 1,286 patients (731 male). Higher PTH associated with inferior EFS in primary malignant brain tumors (HR 1.80 [1.19-2.72]), embryonal (HR 2.20 [1.1-4.43]), and lymphatic malignancies (HR 1.98 [1.05-3.72]). Vitamin D deficiency associated with inferior EFS in embryonal malignancies (HR 2.41 [1.24-4.68]). In a multivariate Cox model, only higher PTH remained significant for inferior EFS. CONCLUSIONS: Elevated PTH may indicate adverse outcomes in certain pediatric cancers. IMPACT: This study identifies elevated parathyroid hormone (PTH) as a potential marker for poor outcomes in pediatric cancer patients, emphasizing the need for adequate vitamin D and calcium management.

Cognitive Symptoms Are Not Associated with Cognitive Performance in Post-Acute mTBI.

OBJECTIVE: Subjective cognitive symptoms are commonly reported after mild traumatic brain injury (mTBI) but are often not associated with objective cognitive performance. This may be due to limitations in traditional cognitive performance measures, which may not be sensitive to subtle variations in cognition in post-acute mTBI. This study explored associations between objective and subjective cognition using computer-based tasks of increasing cognitive load, proposed to be more sensitive to subtle differences in performance. METHOD: Individuals with mTBI (n = 68) and trauma controls (n = 40) were prospectively recruited and assessed approximately 8 weeks post-injury. Participants completed measures of subjective symptom reporting, objective cognitive performance (including two computer-based tasks of increasing cognitive load), and psychological distress. RESULTS: There were no significant associations between subjective and objective cognition reporting in the mTBI group, both in bivariate correlations (|r| = 0.01-0.20, p > .05) and when controlling for psychological distress (|r| = 0.00-0.17, p > .05). A similar pattern of results was observed in trauma controls, suggesting that the limited relationships between objective and subjective cognition in mTBI may not be specific to this population. CONCLUSIONS: Despite employing measures of cognitive performance proposed to be more sensitive than traditional tasks, no significant relationships were observed between objective and subjective cognition in post-acute mTBI, and estimated effect sizes were small to negligible. This provides further evidence that at a group level 8 weeks after mTBI subjective cognitive symptoms primarily reflect factors aside from objective cognition.

Feasibility, efficacy, and safety of animal-assisted activities with visiting dogs in inpatient pediatric oncology.

BACKGROUND: Childhood cancer entails a heavy burden for patients and their families. Recent advances in overall survival rates have increasingly brought long-term quality of life into focus. Animal-assisted activities (AAAs) have long been hypothesized to alleviate the burden on pediatric patients and their peers in the hospital setting. However, their use in inpatient pediatric oncology has been a sensitive issue mainly due to the fear of infections, resulting in a lack of studies. This study presents data on the feasibility, safety, and efficacy of AAAs from a single German center. METHODS: Between 2018 and 2022, 60 patients (median age = 10.3 years) diagnosed with malignancy and undergoing treatment were visited by an intervention dog (total visits = 100). Patients were screened for infections as per hospital policy, with additional microbiological testing performed based on symptoms. The dog was screened for human pathogens and zoonoses. Microbial data and hospitalizations were analyzed from two months prior to the first visit until two months after the last visit. Acceptance of being in the hospital, both with and without planned animal-assisted interventions and pre- and post-intervention state stress, were measured using a validated visual analogue scale (0-10). RESULTS: Patients benefited from AAAs, showing increased acceptance of being in the hospital (median: 7.25 vs. 4.50, P < 0.001) and decreased median state stress ratings one hour after the visit compared to one hour before the visit (1.00 vs. 4.25, P < 0.001). The intervention did not result in an increased number of infections or unplanned hospitalizations, and no zoonoses were detected. All microbial screening tests of the dog were negative. CONCLUSIONS: AAAs with visiting dogs in inpatient pediatric oncology are feasible and safe. Although they hold promise for enhancing patients' well-being, further prospective studies are needed. Supplementary file 2 (MP4 240076 KB).