Sphingosine kills intracellular Pseudomonas aeruginosa and Staphylococcus aureus.

Sphingosine has been previously shown to kill many strains of pathogenic bacteria including Pseudomonas aeruginosa, Staphyloccus aureus, Acinetobacter, and atypical mycobacteria. However, these studies were performed on isolated or extracellular bacteria and it is unknown whether sphingosine also targets intracellular bacteria. Here, we demonstrate that exogenously-added sphingosine directly binds to extracellular P. aeruginosa and S. aureus, but also targets and binds to intracellular bacteria. Intracellular sphingosine and bacteria were identified by sequential immunostainings. We further show that exogenously-added sphingosine also kills intracellular P. aeruginosa and S. aureus using modified gentamycin assays. Intracellular killing of P. aeruginosa and S. aureus by sphingosine is not mediated by improved phagosomal-lysosomal fusion. In summary, our data indicate that sphingosine binds to and most likely also directly kills extra- and intracellular P. aeruginosa and S. aureus.

Symmetry of the left and right tibial plafond; a comparison of 75 distal tibia pairs.

PURPOSE: Tibia plafond or pilon fractures present a high level of complexity, making their surgical management challenging. Three-Dimensional Virtual Planning (3DVP) can assist in preoperative planning to achieve optimal fracture reduction. This study aimed to assess the symmetry of the left and right tibial plafond and whether left-right mirroring can reliably be used. METHODS: Bilateral CT scans of the lower limbs of 75 patients without ankle problems or prior fractures of the lower limb were included. The CT images were segmented to create 3D surface models of the tibia. Subsequently, the left tibial models were mirrored and superimposed onto the right tibia models using a Coherent Point Drift surface matching algorithm. The tibias were then cut to create bone models of the distal tibia with a height of 30 mm, and correspondence points were established. The Euclidean distance was calculated between correspondence points and visualized in a boxplot and heatmaps. The articulating surface was selected as a region of interest. RESULTS: The median left-right difference was 0.57 mm (IQR, 0.38 - 0.85 mm) of the entire tibial plafond and 0.53 mm (IQR, 0.37 - 0.76 mm) of the articulating surface. The area with the greatest left-right differences were the medial malleoli and the anterior tubercle of the tibial plafond. CONCLUSION: The tibial plafond exhibits a high degree of bilateral symmetry. Therefore, the mirrored unfractured tibial plafond may be used as a template to optimize preoperative surgical reduction using 3DVP techniques in patients with pilon fractures.

Prevalence of Rotational Malalignment After Infrapatellar Versus Suprapatellar Intramedullary Nailing of Tibial Shaft Fractures.

Background: Up to 30% of patients with a tibial shaft fracture sustain iatrogenic rotational malalignment (RM) after infrapatellar (IP) nailing. Although IP nailing remains the management of choice for most patients, suprapatellar (SP) nailing has been gaining popularity. It is currently unknown whether SP nailing can provide superior outcomes with regard to tibial RM. The aim of this study was to compare the differences in the prevalence of RM following IP versus SP nailing. Methods: This retrospective study included 253 patients with a unilateral, closed tibial shaft fracture treated with either an IP or SP approach between January 2009 and April 2023 in a Level-I trauma center. All patients underwent a postoperative, protocolized, bilateral computed tomography (CT) scan for RM assessment. Results: RM was observed in 30% and 33% of patients treated with IP and SP nailing, respectively. These results indicate no significant difference (p = 0.639) in the prevalence of RM between approaches. Furthermore, there were no significant differences in the distribution (p = 0.553) and direction of RM (p = 0.771) between the 2 approaches. With the IP and SP approaches, nailing of left-sided tibial shaft fractures resulted in predominantly internal RM (85% and 73%, respectively), while nailing of right-sided tibial shaft fractures resulted in predominantly external RM (90% and 80%, respectively). The intraobserver reliability for the CT measurements was 0.95. Conclusions: The prevalence of RM was not influenced by the entry point of tibial nailing (i.e., IP versus SP). Hence, the choice of surgical approach should rely on factors other than the risk of RM. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Sphingosine Prevents Rhinoviral Infections.

Rhinoviral infections cause approximately 50% of upper respiratory tract infections and novel treatment options are urgently required. We tested the effects of 10 µM to 20 µM sphingosine on the infection of cultured and freshly isolated human cells with minor and major group rhinovirus in vitro. We also performed in vivo studies on mice that were treated with an intranasal application of 10 µL of either a 10 µM or a 100 µM sphingosine prior and after infection with rhinovirus strains 1 and 2 and determined the infection of nasal epithelial cells in the presence or absence of sphingosine. Finally, we determined and characterized a direct binding of sphingosine to rhinovirus. Our data show that treating freshly isolated human nasal epithelial cells with sphingosine prevents infections with rhinovirus strains 2 (minor group) and 14 (major group). Nasal infection of mice with rhinovirus 1b and 2 is prevented by the intranasal application of sphingosine before or as long as 8 h after infection with rhinovirus. Nasal application of the same doses of sphingosine exerts no adverse effects on epithelial cells as determined by hemalaun and TUNEL stainings. The solvent, octylglucopyranoside, was without any effect in vitro and in vivo. Mechanistically, we demonstrate that the positively charged lipid sphingosine binds to negatively charged molecules in the virus, which seems to prevent the infection of epithelial cells. These findings indicate that exogenous sphingosine prevents infections with rhinoviruses, a finding that could be therapeutically exploited. In addition, we demonstrated that sphingosine has no obvious adverse effects on the nasal mucosa. Sphingosine prevents rhinoviral infections by a biophysical mode of action, suggesting that sphingosine could serve to prevent many viral infections of airways and epithelial cells in general. Future studies need to determine the molecular mechanisms of how sphingosine prevents rhinoviral infections and whether sphingosine also prevents infections with other viruses inducing respiratory tract infections. Furthermore, our studies do not provide detailed pharmacokinetics that are definitely required before the further development of sphingosine.

Cast immobilization duration for distal radius fractures, a systematic review.

PURPOSE: The optimal duration of immobilization for the conservative treatment of non- or minimally displaced and displaced distal radius fractures remains under debate. This research aims to review studies of these treatments to add evidence regarding the optimal immobilization period. METHODS: A comprehensive database search was conducted. Studies investigating and comparing short (< 3 weeks) versus long (> 3 weeks) immobilizations for the conservative treatment of distal radius fractures were included. The studies were evaluated for radiological and functional outcomes, including pain, grip strength, and range of motion. Two reviewers independently reviewed all studies and performed the data extraction. RESULTS: The initial database search identified 11.981 studies, of which 16 (involving 1.118 patients) were ultimately included. Patient-reported outcome measurements, grip strength, range of motion, and radiological outcomes were often better after shorter immobilization treatments. Radiological outcomes were better with longer immobilization in two studies and shorter immobilization in one study. Fourteen studies concluded that early mobilization is preferred, while the remaining two studies observed better outcomes with longer immobilization. The data were unsuitable for meta-analysis due to their heterogeneous nature. CONCLUSION: Shorter immobilization for conservatively treated distal radius fractures often yield equal or better outcomes than longer immobilizations. The immobilization for non- or minimally displaced distal radius fractures could therefore be shortened to 3 weeks or less. Displaced and reduced distal radius fractures cannot be immobilized shorter than 4 weeks due to the risk of complications. Future research with homogeneous groups could elucidate the optimal duration of immobilization.

European military surgical teams in combat theater: A survey study on deployment preparation and experience.

INTRODUCTION: Adequate (predeployment) training of the nowadays highly specialized Western military surgical teams is vital to ensure a broad range of surgical skills to treat combat casualties. This survey study aimed to assess the self-perceived preparedness, training needs, deployment experience, and post-deployment impact of surgical teams deployed with the Danish, Dutch, or Finnish Armed Forces. Study findings may facilitate a customized predeployment training. METHODS: A questionnaire was distributed among Danish, Dutch, and Finnish military surgical teams deployed between January 2013 and December 2020 (N = 142). The primary endpoint of self-perceived preparedness ratings, and data on the training needs, deployment experiences, and post-deployment impacts were compared between professions and nations. RESULTS: The respondents comprised 35 surgeons, 25 anesthesiologists, and 39 supporting staff members, with a response rate of 69.7 % (99/142). Self-perceived deployment preparedness was rated with a median of 4.0 (IQR 4.0-4.0; scale: 1 [very unprepared]-5 [more than sufficient]). No differences were found among professions and nations. Skills that surgeons rated below average (median <6.0; scale: 1 [low]-10 [high]) included tropical disease management and maxillofacial, neurological, gynecological, ophthalmic, and nerve repair surgery. The deployment caseload was most often reported as <1 case per week (41/99, 41.4 %). The need for professional psychological help was rated at a median of 1.0 (IQR 1.0-1.0; scale: 1 [not at all]-5 [very much]). CONCLUSIONS: Military surgical teams report overall adequate preparedness for deployment. Challenges remain for establishing broadly skilled teams because of a low deployment caseload and ongoing primary specializations. Additional training and exposure were indicated for several specialism-specific skill areas. The need for specific training should be addressed through customized predeployment programs.