Background: Bucket-handle meniscal tears are mostly treated arthroscopically. However, there is no clear evidence as to whether the time to surgery impacts the outcome and whether or not lesions should be treated urgently. Methods: Sixty patients were interviewed about the current status of their knee with a mean follow-up of 6.1 years (SD = 3.5). Forty-one patients underwent meniscus repair, and fifteen patients received partial resections. The primary outcome was the rate of reoperation after meniscus repair. Secondary outcomes were pain at rest and during exercise, return to sports, and Tegner and Lysholm scores. Results: The average time to surgery was 14.4 days, with no significant impact of surgical timing on the rate of reoperation. Furthermore, no significant differences were found in pain levels, return to sports, or Tegner and Lysholm scores based on the timing of surgery. Conclusions: In our cohort, the time to surgery was not a prognostic factor for the reoperation rate or postoperative outcome in repairing bucket-handle meniscal tears. Therefore, arthroscopic repair should not be performed in an emergency setting but conducted after careful planning by experienced arthroscopy surgeons. Regarding the return to sports, postoperative factors such as rehabilitation protocols or surgical techniques could be more important than the time to surgery.
Background: Post-traumatic joint contracture (PTJC) remains one of the most prevalent and challenging complications arising from musculoskeletal trauma or surgical intervention. Conventional treatment modalities are largely reactive and address symptoms after onset, yet provide limited efficacy once contracture has developed. In contrast, pharmacological strategies targeting the underlying inflammatory and fibrotic pathways offer a promising strategy for preventing the development of PTJC altogether. Methods: A total of 26 male Sprague Dawley rats underwent standardized knee trauma followed by immobilization for a duration of two weeks. Rats were randomized into two groups. The experimental group (n = 13) received bosentan at a dosage of 50 mg/kg twice daily throughout the immobilization period. The control group (n = 13) received a placebo instead. Joint mobility was quantitatively assessed by measuring the contracture angle (CA) and resistance to extension. In addition, posterior joint capsule tissues were harvested for histological analysis and subjected to quantitative PCR (qPCR) to quantify the expression of profibrotic genes, including α-Sma, Il-6, Tgf-β1, Nfκ-b, Ctgf. Results: Bosentan had no relevant effect on the biomechanics of the contracture compared to the placebo group. The contracture angle was comparable between the groups (86.8° ± 14.1°, 84.8° ± 11.1°). Similarly, the force required to achieve knee joint extension was comparable between the groups. Gene expression analysis also provided no evidence of reduced expression of pro-inflammatory or profibrotic genes. Histological assessments revealed no change in the absolute or relative number of myofibroblasts, or in the number of vessels, in the posterior joint capsules of the rats treated with bosentan. Compared to the control group, the number of myofibroblasts significantly increased in both the bosentan and control groups (p < 0.001, one-way ANOVA). Conclusions: Bosentan’s purported antifibrotic properties do not appear to confer a preventative effect on the development of PTJC. These findings suggest that, despite its potential in modulating fibrosis, bosentan does not mitigate the progression of the fibrotic condition. Furthermore, the involvement of endothelin-1 (ET-1) in the pathophysiology of PTJC remains yet to be fully understood, warranting further investigation.
Background: The increasing incidence of spondylodiscitis and its potentially severe consequences when not promptly diagnosed highlight the need for further research to improve treatment guidelines, reduce mortality and morbidity and improve the quality of life in patients who suffer from persistent physical limitations. Methods: We collected data from 103 patients, with 8 patients lost to follow-up, who were diagnosed with vertebral osteomyelitis, disk infection or discitis between 2009 and 2018. The primary outcome was the 1-year mortality rate in patients treated with either conservative or surgical intervention, with both groups receiving antibiotic treatment. A standardized questionnaire was used to assess health-related quality of life after treatment by evaluating the European Quality of Life 5 Dimension 5 Level version (EQ-5D-5L) and the European Quality of Life Visual Analog Scale (EQ-VAS). In addition, we used the Oswestry Disability Index (ODI) and the Parker Mobility Score to identify backpain-related limitations after treatment. Results: The group receiving surgical treatment had a significantly lower 1-year mortality rate (22%) than did those who were treated conservatively, who had a 4-fold greater risk for death after a year following first diagnosis of SD and treatment. With respect to quality of life, 39 patients answered the standardized questionnaires during follow-up, and the questionnaire results revealed no significant difference in limitations in daily life or in health-related quality of life, with a median Parker Mobility Score of 9 for the conservatively treated patients compared with 7.5 for the surgically treated patients. This difference between the groups was not statistically significant, with a p value of 0.216 > α. A similar result was obtained in the evaluation of the ODI, with a medial index of 30% in the conservatively treated group compared with 24% in the surgical group, which was not statistically significant as indicated by a p value of 0.360 > α. Conclusions: The early surgical approach when treating spondylodiscitis is advantageous for identifying the underlying infection and initiating appropriate antibiotic therapy, therefore reducing mortality and resulting in a greater likelihood of full recovery than the conservative treatment does.
The optimal ventilation strategy during cardiopulmonary resuscitation (CPR) has eluded scientists for years. This porcine study aims to validate the hypothesis that ultra-low tidal volume ventilation (tidal volume 2–3 mL kg−1; ULTVV) minimizes renal and hepatic end-organ damage when compared to standard intermittent positive pressure ventilation (tidal volume 8–10 mL kg−1; IPPV) during CPR. After induced ventricular fibrillation, the animals were ventilated using an established CPR protocol. Upon return of spontaneous circulation (ROSC), the follow-up was 20 h. After sacrifice, kidney and liver samples were harvested and analyzed histopathologically using an Endothelial, Glomerular, Tubular, and Interstitial (EGTI) scoring system for the kidney and a newly developed scoring system for the liver. Of 69 animals, 5 in the IPPV group and 6 in the ULTVV group achieved sustained ROSC and were enlisted, while 4 served as the sham group. Creatinine clearance was significantly lower in the IPPV-group than in the sham group (p < 0.001). The total EGTI score was significantly higher for ULTVV than for the sham group (p = 0.038). Aminotransferase levels and liver score showed no significant difference between the intervention groups. ULTVV may be advantageous when compared to standard ventilation during CPR in the short-term ROSC follow-up period.
Background/Objectives: Post-traumatic joint contracture (PTJC) is a common complication in orthopedic surgery characterized by fibrosis and restricted joint mobility. Previous work by our multi-arm study demonstrated that nintedanib monotherapy could effectively mitigate PTJC by targeting fibroblast activation pathways. Since PTJC involves multiple simultaneously activated signaling pathways, we hypothesized that combination therapy targeting both inflammation and fibrosis might be advantageous for improving outcomes. As a candidate for combination treatment with nintedanib, bosentan, an endothelin receptor antagonist that modulates inflammatory responses, was chosen to assess whether this approach could improve the prevention of PTJC. Methods: Thirty-nine Sprague Dawley rats were randomized evenly into three groups after undergoing a standardized hyperextension trauma of the knee and K-wire arthrodesis over a period of two weeks. The experimental groups (n = 13 each) received a combination (COMB) of nintedanib (5 mg/kg/d, twice daily) and bosentan (50 mg/kg/d, twice daily), or nintedanib (5 mg/kg/d, twice daily) alone throughout the immobilization period. The control group (n = 13), meanwhile, was given a placebo. Joint mobility was evaluated quantitatively by measuring the contracture angle (CA) and resistance to extension. Additionally, tissue from the posterior joint capsule was collected for histological analysis. Quantitative PCR was used to analyze tissue and assess the expression levels of genes involved in the pro-fibrotic process, including, Il-6, Tgf-β, Nf-κb, Ctgf, and α-Sma. Statistical analysis involved Kruskal–Wallis and ANOVA tests with post hoc methods, with significance defined at p < 0.05. Results: Both combination therapy and nintedanib monotherapy significantly reduced the contracture angle compared to placebo (p ≤ 0.05 and p ≤ 0.01, respectively), with no significant difference between treatments. Histological analysis showed significantly fewer myofibroblasts in the COMB and nintedanib groups versus placebo (p < 0.05). α-SMA expression was significantly decreased by 8-fold (COMB) and 11-fold (nintedanib) compared to placebo (p < 0.05), with no differences between treatments. No significant differences were detected in upstream pro-fibrotic gene expression among groups. Conclusions: Based on results comparable to those achieved with nintedanib monotherapy, the additional administration of bosentan does not appear to offer any further benefit at the given experimental setup.