The myocutaneous gastrocnemius flap for periprosthetic joint infection of the knee.

Purpose: Periprosthetic joint infection (PJI) following total knee arthroplasty (TKA) presents significant challenges, especially in elderly and comorbid patients, often necessitating revision surgeries. We report on a series of patients with confirmed PJI of the knee and concomitant soft-tissue/extensor apparatus defects, treated by using pedicled myocutaneous medial or lateral sural artery perforator (MSAP/LSAP) gastrocnemius flaps. Methods: Our retrospective study at the Center for Musculoskeletal Infections, included patients with knee PJI undergoing pedicled myocutaneous MSAP/LSAP gastrocnemius flap reconstruction for combined soft tissue and extensor apparatus defects. The tendinous back of the gastrocnemius muscle was used and, if required, the Achilles tendon for extensor apparatus reconstruction, with the skin island addressing the cutaneous defect. Perioperative complications and postoperative outcomes after 1 year were evaluated, including functional and clinical assessments with the American Knee Society Score (AKSS). Results: Eight patients (mean age 73 years; five female) were included, predominantly with Staphylococcus aureus infections. Six patients involved isolated MSAP flaps, two were extended with the Achilles tendon. The median time for wound healing was 9 days. Short-term follow-up showed successful reconstruction in seven patients, with minor wound dehiscence in one patient. One patient required flap revision for a perigenicular haemato-seroma and two patients were diagnosed with new haematogenous PJI infection. Significant improvement in AKSS scores after surgery was observed (functional AKSS: median 33-85; clinical AKSS: median 64-91, p = 0.001). Conclusion: Pedicled myocutaneous MSAP/LSAP gastrocnemius flaps offer a safe, reliable and versatile option for reconstructing combined soft tissue and extensor apparatus defects in PJI after TKA. This approach yields excellent functional outcomes with minimal peri- and postoperative complications, which is particularly beneficial in elderly and comorbid patients and feasible in settings without microsurgical availability. Level of evidence: Level IV.

Impact of Adjuvant Radiotherapy on Free Flap Volume in Autologous Breast Reconstruction: A Scoping Review.

In autologous breast reconstruction, a sufficient flap volume is fundamental to restore breast shape and ensure an aesthetic outcome. After mastectomy, postoperative irradiation is regularly indicated in the oncological treatment algorithm. When administering radiation therapy after autologous reconstruction, the tissue transferred is inherently irradiated. Although there is evidence that points to a reduction in flap volume after adjuvant radiotherapy, the data have been contradicting and inconclusive. To address this anecdotal evidence, we performed a scoping review of the current literature that addresses the effect of radiotherapy on breast flap volume. Six two-armed studies, comprising a total of 462 patients, reported on the effect of adjuvant radiotherapy on free flap volume changes. Of those, two studies found a significant negative impact of radiotherapy on free flap volume, while the other four studies did not. Reported flap volume changes ranged from no change to a reduction of 26.2%, measured up to two years postoperatively. The selected studies contain varying patient numbers, follow-up timepoints, types of flaps, and measuring methods, contributing to a relatively high heterogeneity. While we present some evidence suggesting a significant impact of adjuvant radiotherapy on breast flap volume, future studies are needed to further investigate this potential correlation.

Soft-tissue reconstruction in lower-leg fracture-related infections: An orthoplastic outcome and risk factor analysis.

Introduction Fracture-related infection (FRI) is a severe post-traumatic complication which is occasionally accompanied by a deficient or even avital soft-tissue envelope. In these cases, a thoroughly planned orthoplastic approach is imperative as a vital and intact soft-tissue envelope is mandatory to achieve fracture union and infection eradication. The aim of this study was, to analyse if soft-tissue reconstruction (STR) without complications is associated with a better long-term outcome compared to FRI patients with STR complications. In particular, it was investigated if primary flap failure represented a risk factor for compromised fracture union and recurrence of infection. Patients and Methods Patients with a lower leg FRI requiring STR (local, pedicled and free flaps) who were treated from 2010-18 at the University Hospital Basel were included in this retrospective analysis. The main outcome measure was the success rate of STR, further outcome measures were fracture nonunion and recurrence of infection. Results Overall, 145 patients with lower leg FRI were identified, of whom 58 (40%) received STR (muscle flaps: n = 38, fascio-cutaneous flaps: n=19; composite osteo-cutaneous flap: n = 1). In total seven patients required secondary STR due to primary flap failure. All failures and flap-related complications occurred within the first three weeks after surgery. Secondary STR was successful in all cases. A high Charlson Comorbidity Index Score was a significant risk factor for flap failure (p = 0.011). Out of the 43 patients who completed the 9-month follow-up, 11 patients presented with fracture nonunion and 12 patients with a recurrent infection. Polymicrobial infection was a significant risk factor for fracture nonunion (p = 0.002). Primary flap failure was neither a risk factor for compromised fracture consolidation (p = 0.590) nor for recurrence of infection (p = 0.508). Conclusion: A considerable number of patients with lower-leg FRI required STR. This patient subgroup is complex and rich in complications and the long-term composite outcome demonstrated a high rate of compromised fracture consolidation and recurrent infections. It appears that secondary STR should be performed, as primary flap failure was neither a risk factor for compromised fracture consolidation nor for recurrence of infection. We propose to monitor these patients closely for three weeks after STR.

Importance of Cullin4 Ubiquitin Ligase in Malignant Pleural Mesothelioma.

Neurofibromatosis type 2 (NF2), the tumor suppressor frequently lost in malignant pleural mesothelioma (MPM), suppresses tumorigenesis in part by inhibiting the Cullin4 ubiquitin ligase (CUL4) complex in the nucleus. Here, we evaluated the importance of CUL4 in MPM progression and tested the efficacy of cullin inhibition by pevonedistat, a small molecule inhibiting cullin neddylation. CUL4 paralogs (CUL4A and CUL4B) were upregulated in MPM tumor specimens compared to nonmalignant pleural tissues. High gene and protein expressions of CUL4B was associated with a worse progression-free survival of MPM patients. Among 13 MPM cell lines tested, five (38%) were highly sensitive to pevonedistat (half maximal inhibitory concentration of cell survival IC50 < 0.5 µM). This remained true in a 3D spheroid culture. Pevonedistat treatment caused the accumulation of CDT1 and p21 in both sensitive and resistant cell lines. However, the treatment induced S/G2 cell cycle arrest and DNA rereplication predominantly in the sensitive cell lines. In an in vivo mouse model, the pevonedistat treatment significantly prolonged the survival of mice bearing both sensitive and resistant MPM tumors. Pevonedistat treatment reduced growth in sensitive tumors but increased apoptosis in resistant tumors. The mechanism in the resistant tumor model may be mediated by reduced macrophage infiltration, resulting from the suppression of macrophage chemotactic cytokines, C-C motif chemokine ligand 2 (CCL2), expression in tumor cells.