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Dominik Herzog,1 Werner Vach,2,3 Thomas Schwamborn,2 Franziska Saxer1,3,4 1Faculty of Medicine, University of Basel, Basel, Switzerland; 2Crossklinik Basel, Basel, Switzerland; 3Basel Academy for Quality and Research in Medicine, Basel, Switzerland; 4Novartis BioMedical Research, Translational Medicine, Basel, SwitzerlandCorrespondence: Franziska Saxer, Faculty of Medicine, University of Basel, Klingelbergstrasse 61, Basel, 4056, Switzerland, Tel +41 61 207 31 11, Email franziska.saxer@unibas.chIntroduction: Anterior cruciate ligament (ACL) ruptures are frequent injuries, especially in athletes. Return to sports after reconstruction of the ligament is a frequently debated topic and of high relevance for these patients. It is mostly achieved at 9– 12 months post-surgery. However, the risk of subsequent knee injuries is high and psychological factors play an important role in the process and success of returning to sports. Little is known about patients’ perception of their journey returning to sports. This study aims to fill the gap.Material and Methods: The study aimed to include patients treated surgically for an ACL injury over 5 years at a specialized sports-medicine clinic. Patients were surveyed on the impact of the injury on their lives, their return to sports experience, and medical history.Results: In total, 100 (of 474) patients aged 35.9 years responded. Within 5 years, 19% experienced a reoperation and 23% a new knee injury. Overall, 83% of patients returned to their main sport, 72% reached their pre-injury level. However, 45% reported at least one distinct or severe consequence of their ACL injury. The ability to return to sports had more impact on the perception of the course of treatment than the experience of new injuries or surgery.Conclusion: The rate of successful return to sports was comparable to previous reports despite a higher average age in this cohort. A successful return to sports seems to be a major determinant for the perception of impact from the injury and may be more important than the avoidance of repeat trauma.Keywords: knee injury, patient journey, psychological impact of injury, quality of life, treatment perception

Over the last decades, Pinus taeda L. plantations in southern Brazil showed a great increase in average production. However, the gains in productivity obtained by genetic selection and breeding have nowadays stabilized. Research on edaphic factors and silvicultural practices is currently performed with the aim of both increasing the productivity of P. taeda plantations and maintaining the soil quality. To this end, soil microbiological attributes are considered better indicators of soil quality as they are more sensitive than chemical and physical ones. In this study, we aimed to evaluate the relationship between microbial activity and the physical and chemical parameters of different soil types under young Pinus taeda plantations at five different sites in southern Brazil. Soil samples were collected at depths of 0-5 and 5-10 cm. The soil microbiological attributes evaluated were: potentially mineralizable nitrogen (PMN), microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), microbial basal respiration (MBR), and metabolic quotient (qCO2). We also evaluated some physical and chemical soil parameters. Sites with the highest values of C, clay, and nutrients in the soil, showed higher values for the soil microbiological attributes, compared to the other study sites. The previous management with minimal tillage in some sites seems to positively affect soil quality. The MCB and MBR showed better sensitivity in indicating differences between sites and showed a good relationship with clay content, C/N ratio, K, and pH. These results suggest that site-specific characteristics such as soil type or forest management influence soil microbiological attributes in Pinus taeda plantations during initial growth in southern Brazil.

Emergency Medicine physicians experience a significant number of interruptions throughout their work day. One common cause of interruptions is the immediate interpretation of triage electrocardiograms (ECGs). Recent studies have suggested that ECGs interpreted as normal via automated analysis by the ECG machine rarely require urgent cardiac intervention and suggested that providers may not have to be interrupted to interpret these "normal" ECGs. We describe the case of a patient who presented to the Emergency Department (ED) with chest pain and an ECG interpreted as normal by an automated reading from the ECG machine, despite having acute coronary syndrome requiring emergent intervention., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests and have recieved no funding., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background : Humanitarian aid workers (HAWs) are indirectly exposed to atrocities relating to people of concern (POC). This may result in a risk of secondary traumatization demonstrated by post-traumatic stress symptoms (PTSSs). Previous studies have demonstrated that hemispheric lateralization (HL) moderates the relationship between threat exposure and post-traumatic stress symptoms (PTSSs). Aims : We hypothesized that indirect exposure to atrocities (IETA) would be positively correlated with PTSSs among HAWs with right and not left HL. Method : Fifty-four HAWs from several countries that provided humanitarian support in Greece and Colombia participated in this correlational and cross-sectional observation study. They completed scales relating to IETA, PTSSs were assessed using a brief, valid scale, and HL was measured. Results : IETA was positively and significantly related to PTSSs (r = 0.39, p < 0.005). Considering HL, IETA was unrelated to PTSSs among people with right HL (r = 0.29, p = 0.14), while IETA was related to PTSSs among people with left HL (r = 0.52, p = 0.008). Right HL emerged as a protective factor in the relationship between IETA and PTSS. Conclusions : An assessment of dominant HL can serve as one consideration among others when deploying HAWs in specific locations and roles, vis à vis IETA. Moreover, those found to have a higher risk for PTSSs based on their HL could be monitored more closely to prevent adverse reactions to IETA.

The targeted or universal decolonization of patients through octenidine for nasal treatment and antiseptic body wash for 3 to 5 days prior elective surgery has been implemented in several surgical disciplines in order to significantly reduce surgical site infections (SSIs) caused by Staphylococcus aureus carriage. However, as most healthcare facilities also screen patients on admission for pilot infection, it is imperative that a prophylactic nasal decolonization procedure not yield a false negative SARS-CoV-2 status in otherwise positive patients. We assessed the effect of a commercially available octenidine-containing nasal gel on two different screening methods-antigen (Ag) detection based on colloidal gold immunochromatography and RT-PCR-in a prospective-type accuracy pilot study in asymptomatic SARS-CoV-2-positive inpatients. All patients still showed a positive test result after using the octenidine-containing nasal gel for about 3 days; therefore, its application did not influence SARS-CoV-2 screening, which is of high clinical relevance. Of note is that Ag detection was less sensitive, regardless of the presence of octenidine. From an infection prevention perspective, these results favor octenidine-based decolonization strategies, even during seasonal SARS-CoV-2 periods. As only asymptomatic patients are considered for elective interventions, screening programs based on RT-PCR technology should be preferred.

Background: Children and young adults with medical complexity (CMC) experience high rates of healthcare reutilization following hospital discharge. Prior studies have identified common hospital-to-home transition failures that may increase the risk for reutilization, including medication, technology and equipment issues, financial concerns, and confusion about which providers can help with posthospitalization needs. Few interventions have been developed and evaluated for CMC during this transition period., Objective: We will compare the effectiveness of the garnering effective telehealth 2 help optimize multidisciplinary team engagement (GET2HOME) transition bundle intervention to the standard hospital-based care coordination discharge process by assessing healthcare reutilization and patient- and family-centered outcomes., Designs, Settings, and Participants: We will conduct a pragmatic 2-arm randomized controlled trial (RCT) comparing the GET2HOME bundle intervention to the standard hospital-based care discharge process on CMC hospitalized and discharged from hospital medicine at two sites of our pediatric medical center between November 2022 and February 2025. CMC of any age will be identified as having complex chronic disease using the Pediatric Medical Complexity Algorithm tool. We will exclude CMC who live independently, live in skilled nursing facilities, are in custody of the county, or are hospitalized for suicidal ideation or end-of-life care., Intervention: We will randomize participants to the bundle intervention or standard hospital-based care coordination discharge process. The bundle intervention includes (1) predischarge telehealth huddle with inpatient providers, outpatient providers, patients, and their families; (2) care management discharge task tracker; and (3) postdischarge telehealth huddle with similar participants within 7 days of discharge. As part of the pragmatic design, families will choose if they want to complete the postdischarge huddle. The standard hospital-based discharge process includes a pharmacist, social worker, and care management support when consulted by the inpatient team but does not include huddles between providers and families., Main Outcome and Measures: Primary outcome will be 30-day urgent healthcare reutilization (unplanned readmission, emergency department, and urgent care visits). Secondary outcomes include 7-day urgent healthcare reutilization, patient- and family-reported transition quality, quality of life, and time to return to baseline using electronic health record and surveys at 7, 30, 60, and 90 days following discharge. We will also evaluate heterogeneity of treatment effect for the intervention across levels of financial strain and for CMC with high-intensity neurologic impairment. The primary analysis will follow the intention-to-treat principle with logistic regression used to study reutilization outcomes and generalized linear mixed modeling to study repeated measures of patient- and family-reported outcomes over time., Results: This pragmatic RCT is designed to evaluate the effectiveness of enhanced discharge transition support, including telehealth huddles and a care management discharge tool, for CMC and their families. Enrollment began in November 2022 and is projected to complete in February 2025. Primary analysis completion is anticipated in July 2025 with reporting of results following., (© 2023 Society of Hospital Medicine.)

Skeletal muscle is highly regenerative and is mediated by a population of migratory adult muscle stem cells (muSCs). Effective muscle regeneration requires a spatio-temporally regulated response of the muSC population to generate sufficient muscle progenitor cells that then differentiate at the appropriate time. The relationship between muSC migration and cell fate is poorly understood and it is not clear how forces experienced by migrating cells affect cell behaviour. We have used zebrafish to understand the relationship between muSC cell adhesion, behaviour and fate in vivo . Imaging of pax7-expressing muSCs as they respond to focal injuries in trunk muscle reveals that they migrate by protrusive-based means. By carefully characterizing their behaviour in response to injury we find that they employ an adhesion-dependent mode of migration that is regulated by the RhoA kinase ROCK. Impaired ROCK activity results in reduced expression of cell cycle genes and increased differentiation in regenerating muscle. This correlates with changes to focal adhesion dynamics and migration, revealing that ROCK inhibition alters the interaction of muSCs to their local environment. We propose that muSC migration and differentiation are coupled processes that respond to changes in force from the environment mediated by RhoA signalling.

Diadenosine polyphosphates (Ap n As) are non-canonical nucleotides whose cellular concentrations increase during stress and are therefore termed alarmones, signaling homeostatic imbalance. Their cellular role is poorly understood. In this work, we assessed Ap n As for their usage as cosubstrates for protein AMPylation, a post-translational modification in which adenosine monophosphate (AMP) is transferred to proteins. In humans, AMPylation mediated by the AMPylator FICD with ATP as a cosubstrate is a response to ER stress. Herein, we demonstrate that Ap 4 A is proficiently consumed for AMPylation by FICD. By chemical proteomics using a new chemical probe, we identified new potential AMPylation targets. Interestingly, we found that AMPylation targets of FICD may differ depending on the nucleotide cosubstrate. These results may suggest that signaling at elevated Ap 4 A levels during cellular stress differs from when Ap 4 A is present at low concentrations, allowing response to extracellular cues., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Fibroblasts are the most abundant stromal constituents of the tumour microenvironment in primary as well as metastatic colorectal cancer (CRC). Their supportive effect on tumour cells is well established. There is growing evidence that stromal fibroblasts also modulate the immune microenvironment in tumours. Here, we demonstrate a difference in fibroblast-mediated immune modulation between primary CRC and peritoneal metastasis. Cancer-associated fibroblasts (CAFs) were isolated from primary cancer and from peritoneal metastases (MAFs) from a total of 17 patients. The ectoenzyme CD38 was consistently expressed on the surface of all MAFs, while it was absent from CAFs. Furthermore, MAFs secreted higher levels of IGFBP2, CXCL2, CXCL6, CXCL12, PDGF-AA, FGFb, and IL-6. This was associated with a decreased activation of macrophages and a suppression of CD25 expression and proliferation of co-cultivated T-cells. Downregulation of IGFBP2 abolished these immunosuppressive effects of MAFs. Taken together, these results show that MAFs contribute to an immunosuppressive tumour microenvironment in CRC metastases by modulating the phenotype of immune cells through an IGFBP2-dependent mechanism., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The tumor suppressor protein fragile histidine triad (Fhit) is known to be associated with genomic instability and apoptosis. The tumor-suppressive function of Fhit depends on the interaction with the alarmone diadenosine triphosphate (Ap 3 A), a noncanonical nucleotide whose concentration increases upon cellular stress. How the Fhit-Ap 3 A complex exerts its signaling function is unknown. Here, guided by a chemical proteomics approach employing a synthetic stable Fhit-Ap 3 A complex, we found that the Fhit-Ap 3 A complex, but not Fhit or Ap 3 A alone, impedes translation. Our findings provide a mechanistic model in which Fhit translocates from the nucleolus into the cytosol upon stress to form an Fhit-Ap 3 A complex. The Fhit-Ap 3 A complex impedes translation both in vitro and in vivo , resulting in reduced cell viability. Overall, our findings provide a mechanistic model by which the tumor suppressor Fhit collaborates with the alarmone Ap 3 A to regulate cellular proliferation.

Objective: To evaluate the efficacy of intracervical injection of liposomal bupivacaine for postoperative pain control among women undergoing minimally invasive supracervical hysterectomy., Methods: A randomized double-blinded placebo-controlled trial of intracervical injection of combination liposomal bupivacaine and bupivacaine for postoperative pain among patients undergoing laparoscopic and robotic supracervical hysterectomy. Patients were enrolled between October 1, 2018 and April 30, 2019. The primary outcome was pain at 12 hours postoperatively using a numeric rating scale from zero to 10. Pain scores were also recorded pre-operatively, immediately postoperatively, at 12, 24, and 48 hours postoperatively. The secondary outcome was the number of patients who required opioid analgesic medications up to 48 hours postoperatively., Results: Sixty participants were randomized into the control (n = 30) and intervention (n = 30) groups. Pain scores were 1 and 1.75 (p = 0.89) immediately postoperatively, 3 and 3.5 (p = 0.85) at 12 hours, 3.5 and 5 (p = 0.22) at 24 hours, and 2.75 and 4 (p = 0.18) at 48 hours for the control and intervention groups, respectively. Within the first 24 hours, 10 patients in the control and 14 patients in the intervention group used narcotics (p = 0.37). From the 24 to 48 hours window, 6 and 8 patients in the control and intervention groups used narcotics (p = 0.74), respectively., Conclusion: There was no statistically significant difference in pain scores between patients receiving combination liposomal bupivacaine and bupivacaine intracervical block and those receiving placebo in the first 48 hours after surgery. There was no difference in analgesic use between the two study groups., (© 2022 by SLS, Society of Laparoscopic & Robotic Surgeons.)