Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution

Rationale: Trauma, surgery, and infection can cause severe inflammation. Both dysregulated inflammation intensity and duration can lead to significant tissue injuries, organ dysfunction, mortality, and morbidity. Anti-inflammatory drugs such as steroids and immunosuppressants can dampen inflammation intensity, but they derail inflammation resolution, compromise normal immunity, and have significant adverse effects. The natural inflammation regulator mesenchymal stromal cells (MSCs) have high therapeutic potential because of their unique capabilities to mitigate inflammation intensity, enhance normal immunity, and accelerate inflammation resolution and tissue healing. Furthermore, clinical studies have shown that MSCs are safe and effective. However, they are not potent enough, alone, to completely resolve severe inflammation and injuries. One approach to boost the potency of MSCs is to combine them with synergistic agents. We hypothesized that alpha-1 antitrypsin (A1AT), a plasma protein used clinically and has an excellent safety profile, was a promising candidate for synergism. Methods: This investigation examined the efficacy and synergy of MSCs and A1AT to mitigate inflammation and promote resolution, using in vitro inflammatory assay and in vivo mouse acute lung injury model. The in vitro assay measured cytokine releases, inflammatory pathways, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs) production by neutrophils and phagocytosis in different immune cell lines. The in vivo model monitored inflammation resolution, tissue healing, and animal survival. Results: We found that the combination of MSCs and A1AT was much more effective than each component alone in i) modulating cytokine releases and inflammatory pathways, ii) inhibiting ROS and NETs production by neutrophils, iii) enhancing phagocytosis and, iv) promoting inflammation resolution, tissue healing, and animal survival. Conclusion: These results support the combined use of MSCs, and A1AT is a promising approach for managing severe, acute inflammation

Complications after hip arthroplasty and the association with hospital procedure volume: A nationwide retrospective cohort study on 50,080 total hip replacements with a follow-up of 3 months after surgery

Background and purpose: It has been suggested that a higher procedure volume is associated with less complications af

Day-case open reduction for developmental dysplasia of the hip.

AIMS: Open reduction in developmental dysplasia of the hip (DDH) is regularly performed despite screening programmes, due to failure of treatment or late presentation. A protocol for open reduction of DDH has been refined through collaboration between surgical, anaesthetic, and nursing teams to allow same day discharge. The objective of this study was to determine the safety and feasibility of performing open reduction of DDH as a day case. METHODS: A prospectively collected departmental database was visited. All consecutive surgical cases of DDH between June 2015 and March 2020 were collected. Closed reductions, bilateral cases, cases requiring corrective osteotomy, and children with comorbidities were excluded. Data collected included demographics, safety outcome measures (blood loss, complications, readmission, reduction confirmation), and feasibility for discharge according to the Face Legs Activity Cry Consolidability (FLACC) pain scale. A satisfaction questionnaire was filled by the carers. Descriptive statistics were used for analysis. RESULTS: Out of 168 consecutive DDH cases, 16 patients fit the inclusion criteria (age range 10 to 26 months, 13 female). Intraoperative blood loss ranged from "minimal" to 120 ml, and there were no complications or readmissions. The FLACC score was 0 for all patients. The carers satisfaction questionnaire expressed high satisfaction from the experience with adequate information and support provided. CONCLUSION: Open reduction in DDH, without corrective osteotomy, is safe and feasible to be managed as a day case procedure. It requires a clear treatment pathway, analgesia, sufficient counselling, and communication with carers. It is even more important during the COVID-19 pandemic when reduced length of hospital stay is likely to be safer for both patient and their parents. Cite this article: Bone Joint Open 2021;2(4):271-277

Low risk of thromboembolic complications after fast-track hip and knee arthroplasty

BACKGROUND AND PURPOSE: Pharmacological prophylaxis can reduce the risk of deep venous thrombosis (DVT), pulmonary embolism (PE), and death, and it is recommended 10–35 days after total hip arthroplasty (THA) and at least 10 days after total knee arthroplasty (TKA). However, early mobilization might also reduce the risk of DVT and thereby the need for prolonged prophylaxis, but this has not been considered in the previous literature. Here we report our results with short-duration pharmacological prophylaxis combined with early mobilization and reduced hospitalization.PATIENTS AND METHODS: 1,977 consecutive, unselected patients were operated with primary THA, TKA, or bilateral simultaneous TKA (BSTKA) in a well-described standardized fast-track set-up from 2004–2008. Patients received DVT prophylaxis with low-molecular-weight heparin starting 6–8 h after surgery until discharge. All re-admissions and deaths within 30 and 90 days were analyzed using the national health register, concentrating especially on clinical DVT (confirmed by ultrasound and elevated D-dimer), PE, or sudden death. Numbers were correlated to days of prophylaxis (LOS).RESULTS: The mean LOS decreased from 7.3 days in 2004 to 3.1 days in 2008. 3 deaths (0.15%) were associated with clotting episodes and overall, 11 clinical DVTs (0.56%) and 6 PEs (0.30%) were found. The vast majority of events took place within 30 days; only 1 death and 2 DVTs occurred between 30 and 90 days. During the last 2 years (854 patients), when patients were mobilized within 4 h postoperatively and the duration of DVT prophylaxis was shortest (1–4 days), the mortality was 0% (95% CI: 0–0.5). Incident cases of DVT in TKA was 0.60% (CI: 0.2–2.2), in THA it was 0.51% (CI: 0.1–1.8), and in BSTKA it was 0% (CI: 0–2.9). Incident cases of PE in TKA was 0.30% (CI: 0.1–1.7), in THA it was 0% (CI: 0–1.0), and in BSTKA it was 0% (CI: 0–2.9).INTERPRETATION: The risk of clinical DVT, and of fatal and non-fatal PE after THA and TKA following a fast-track set-up with early mobilization, short hospitalization, and short duration of DVT prophylaxis compares favorably with published regimens with extended prophylaxis (up to 36 days) and hospitalization up to 11 days. This calls for a reconsideration of optimal duration of chemical thromboprophylaxis.</p

Demographic Distribution of Foot and Ankle Surgeries Among Orthopaedic Surgeons and Podiatrists: A 10-Year Database Retrospective Study

Background: Foot and ankle surgeries in the United States (US) are currently performed by orthopaedic surgeons or podiatrists with specialty surgical training. With the trend in healthcare now placing increased emphasis on quality and standardizing patient care, this study aimed to characterize the distribution, volume, and trends of certain foot and ankle surgeries performed in the US by both orthopaedic surgeons and podiatrists. Materials and Methods: A retrospective analysis was performed using the Marketscan Claims Database (Truven Health Analytics, Ann Arbor, Michigan) which covers most privately insured patients under the age of 65 in the USA from 2005 to 2014. We searched current procedural terminology (CPT) codes for total ankle replacement (TAR), triple arthrodesis, hallux valgus correction, pilon fracture open reduction and internal fixation (ORIF), calcaneus fracture ORIF, and ankle fracture ORIF. We recorded the timing and nature of procedures along with various features associated with the surgeon and the geographic location of the treatment facility. Results: We found that the number of foot and ankle procedures performed annually is steadily increasing. Orthopaedic surgeons are the main treating surgeon for common foot and ankle traumatic conditions or complex hind foot cases like TAR. On the other hand, our study showed that podiatrists perform almost 9 out of 10 hallux valgus correction surgeries. Discussion: Our study showed the trends in surgical volumes and differences between surgical podiatrists and orthopaedic surgeons and the evolution of these volumes over a ten year period and differences in surgical repertoire between orthopaedists and podiatrists. Levels of Evidence: Level IV: Case series, Clinical research </jats:p