Is There a Disadvantage to Early Physical Therapy After Multiligament Surgery for Knee Dislocation? A Pilot Randomized Clinical Trial.

BACKGROUND: Multiligament knee injuries, though rare, can be profoundly disabling. Surgeons disagree about when to initiate rehabilitation after surgical reconstruction due to the conflicting priorities of postoperative stability and motion. QUESTIONS/PURPOSES: (1) Does early or late initiation of physical therapy after multiligament knee surgery result in fewer postoperative manipulations? (2) Does early versus late physical therapy compromise stability postoperatively? (3) Does early initiation of physical therapy result in improved patient-reported outcomes, as measured by the Multi-ligament Quality of Life (ML-QOL) score? METHODS: Between 2011 and 2016, 36 adults undergoing multiligament repair or reconstruction were prospectively enrolled in a randomized controlled trial and randomized 1:1 to either early rehabilitation or late rehabilitation after surgery. Eligibility included those with an injury to the posterior cruciate ligament (PCL) and at least one other ligament, as well as the ability to participate in early rehabilitation. Patients who were obtunded or unable to adhere to the protocols for other reasons were excluded. Early rehabilitation consisted of initiating a standardized physical therapy protocol on postoperative day 1 involving removal of the extension splint for quadriceps activation and ROM exercises. Late rehabilitation consisted of full-time immobilization in an extension splint for 3 weeks. Following this 3-week period, both groups engaged in the same standardized physical therapy protocol. All surgical reconstructions were performed at a single center by one of two fellowship-trained sports orthopaedic surgeons, and all involved allograft Achilles tendon PCL reconstruction. When possible, hamstring autograft was used for ACL and medial collateral ligament reconstructions, whereas lateral collateral ligament and posterolateral reconstruction was performed primarily with allograft. The primary outcome was the number of patients undergoing manipulation during the first 6 months. Additional outcomes added after trial registration were patient-reported quality of life scores (ML-QOL) at 1 year and an objective assessment of laxity through a physical examination and stress radiographs at 1 year. One patient from each group was not assessed for laxity or ROM at 1 year, and one patient from each group did not complete the ML-QOL questionnaires. No patient crossover was observed. RESULTS: With the numbers available, there was no difference in the use of knee manipulation during the first 6 months between the rehabilitation groups: 1 of 18 patients in the early group and 4 of 18 patients in the late group (p = 0.34). Similarly, there were no differences in knee ROM, stability, or patient-reported quality of life (ML-QOL) between the groups at 1 year. CONCLUSION: With the numbers available in this study, we were unable to demonstrate a difference between early and late knee rehabilitation with regard to knee stiffness, laxity, or patient-reported quality of life outcomes. The results of this small, randomized pilot study suggest a potential role for early rehabilitation after multiligament reconstruction for knee dislocation, which should be further explored in larger multi-institutional studies. LEVEL OF EVIDENCE: Level II, therapeutic study.

Pediatric central nervous system solitary fibrous tumor: case report.

INTRODUCTION: Solitary fibrous tumors are mesenchymally derived masses most commonly originating from the lung pleura. CASE REPORT: Herein, we report a 6-month-old presenting with syndrome of inappropriate antidiuretic hormone secretion (SIADH) and a suprasellar mass. The mass proved to be a solitary fibrous tumor. This case and salient literature are reviewed. CONCLUSIONS: To our knowledge, this is the youngest patient to be described with a mass of this type within the central nervous system.

Early Compared with Delayed Reconstruction in Multiligament Knee Injury: A Retrospective Propensity Analysis.

BACKGROUND: The purpose of this study was to compare outcomes following early compared with delayed reconstruction in patients with multiligament knee injury (MLKI). METHODS: A retrospective cohort analysis of patients with MLKI from 2007 to 2019 was conducted. Patients who underwent a reconstructive surgical procedure with ≥12 months of postoperative follow-up were included. Patients were stratified into early reconstruction (<6 weeks after the injury) and delayed reconstruction (12 weeks to 2 years after the injury). Multivariable regression models with inverse probability of treatment weighting (IPTW) were utilized to compare the timing of the surgical procedure with the primary outcome (the Multiligament Quality of Life questionnaire [MLQOL]) and the secondary outcomes (manipulation under anesthesia [MUA], Kellgren-Lawrence [KL] osteoarthritis grade, knee laxity, and range of motion). RESULTS: A total of 131 patients met our inclusion criteria, with 75 patients in the early reconstruction group and 56 patients in the delayed reconstruction group. The mean time to the surgical procedure was 17.6 days in the early reconstruction group compared with 280 days in the delayed reconstruction group. The mean postoperative follow-up was 58 months. The early reconstruction group, compared with the delayed reconstruction group, included more lateral-sided injuries (49 patients [65%] compared with 23 [41%]; standardized mean difference [SMD], 0.44) and nerve injuries (36 patients [48%] compared with 9 patients [16%]; SMD, 0.72), and had a higher mean Schenck class (SMD, 0.57). After propensity adjustment, we found no difference between early and delayed reconstruction across the 4 MLQOL domains (p > 0.05). Patients in the early reconstruction group had higher odds of requiring MUA compared with the delayed reconstruction group (24 [32%] compared with 8 [14%]; IPTW-adjusted odds ratio [OR], 3.85 [95% confidence interval (CI), 2.04 to 7.69]; p < 0.001) and had less knee flexion at the most recent follow-up (ß, 6.34° [95% CI, 0.91° to 11.77°]; p = 0.023). Patients undergoing early reconstruction had lower KL osteoarthritis grades compared with patients in the delayed reconstruction group (OR, 0.46 [95% CI, 0.29 to 0.72]; p < 0.001). There were no differences in clinical laxity between groups. CONCLUSIONS: Early reconstruction of MLKIs likely increases the likelihood of postoperative arthrofibrosis compared with delayed reconstruction, but it may be protective against the development of osteoarthritis. When considering the timing of MLKI reconstruction, surgeons should consider the benefit that early reconstruction may convey on long-term outcomes but should caution patients regarding the possibility of requiring an MUA. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Ex vivo adenoviral vector gene delivery results in decreased vector-associated inflammation pre- and post-lung transplantation in the pig.

Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1ß levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function.

Kinetics of lactate metabolism during acellular normothermic ex vivo lung perfusion.

BACKGROUND: Plasma lactate has been used as a marker of poor prognosis in clinical conditions. However, the relationship between lactate production and lung function during acellular normothermic ex vivo lung perfusion (EVLP) is unclear. We investigated the kinetics of lactate metabolism during EVLP and the correlation of this marker with outcomes after transplant. METHODS: Human donor lungs in our clinical EVLP trial (CLs; n = 28) and rejected donor lungs for experimental use (Els; n = 8) were perfused ex vivo using the Toronto technique. Lactate level, lactate/pyruvate (L/P) ratio, and glucose level in the perfusate were measured. In CLs, we examined the relationship between lactate metabolism during EVLP and early post-transplant outcomes. The hypoxia-inducible factor 1 sub-unit 1α (HIF-1α) level in lung tissue was examined in ELs. RESULTS: We performed double-lung EVLP in CLs and single-lung EVLP in ELs. In CLs, the lactate and L/P ratios at the end of EVLP had no correlation with early post-transplant outcomes despite lactate elevation during EVLP. Although lactate elevation was also present in all ELs, we were able to identify 2 groups based on L/P ratio at the end of EVLP. The group with the high L/P ratio had higher airway pressure during EVLP and higher HIF-1α in lung tissue at the end of EVLP. CONCLUSIONS: Lactate increases seen in the EVLP perfusate most often represent physiologic lactate production by the lung in a setting with reduced lactate clearance. Thus, patients who underwent transplantation after EVLP had good outcomes despite lactate elevation during EVLP.

Long pentraxin PTX3 deficiency worsens LPS-induced acute lung injury.

OBJECTIVE: Long pentraxin PTX3 is an inflammatory mediator and a component of the humoral arm of innate immunity. PTX3 expression is increased in animals with acute lung injury (ALI) and in patients with sepsis or acute respiratory distress syndrome and is considered to be a potential biomarker for these diseases. However, the role of PTX3 in the pathogenesis of ALI is not fully understood. We hypothesized that PTX3, as an important immune modulator, may determine the severity of ALI. METHODS: Lipopolysaccharide (LPS) was intra-tracheally administrated to PTX3 knock-out (PTX3-KO) and wild-type (WT) mice. Lung injury, neutrophil infiltration, cell death, fibrin deposition, and tissue factor expression in the lung were determined. Local and systemic inflammatory responses were assessed by measuring cytokines in the lung and plasma. RESULTS: LPS instillation induced ALI in both PTX3-KO and WT mice. Interestingly, PTX3 deficiency significantly increased the magnitude/extent of lung injury compared to that in WT mice. The severe lung injury was accompanied by elevated neutrophil infiltration, cell death, and fibrin deposition in the lung. PTX3 deficiency also enhanced LPS-induced tissue factor expression/activation in the lung and increased tumor necrosis factor-alpha and monocyte chemoattractant protein-1 levels in the plasma. CONCLUSION: Our data suggest that the endogenously expressed PTX3 plays a protective role in the pathogenesis of ALI and that a lack of PTX3 may enhance neutrophil recruitment, cell death, activation of coagulation cascades, and inflammatory responses in the lung.

Technique for prolonged normothermic ex vivo lung perfusion.

BACKGROUND: The inhibition of cellular metabolism induced by hypothermia obviates the possibility of substantial reparative processes occurring during organ preservation. The aim of this study was to develop a technique of extended (12-hour) ex vivo lung perfusion (EVLP) at normothermia for assessment and protective maintenance of the donor lung. METHODS: Six double-lung blocks from 35-kg pigs and 5 single human lungs were subjected to 12 hours of normothermic EVLP using acellular Steen Solution. In the animal studies, the left lung was transplanted into recipients at the end of EVLP and reperfused for 4 hours to evaluate the impact of prolonged EVLP on post-transplant lung function. A protective mode of mechanical ventilation with controlled perfusion flows and pressures in the pulmonary vasculature were employed during EVLP. Lung oxygenation capacity (DeltaPo(2)), pulmonary vascular resistance and airway pressures were evaluated in the system. Red blood cells were added to the perfusate to a hematocrit of 20% at the end of human lung EVLP to study lung functional assessment with and without cells. RESULTS: Lung function was stable during 12 hours of EVLP. This stability during prolonged normothermic EVLP translated into excellent post-transplant lung function (Pao(2)/Fio(2): 527 +/- 22 mm Hg), low edema formation (wet/dry ratio: 5.24 +/- 0.38) and preserved lung histology after transplantation. The acellular perfusion assessment of lung function accurately correlated with post-transplant graft function. CONCLUSIONS: Twelve hours of EVLP at physiologic temperatures using an acellular perfusate is achievable and maintains the donor lungs without inflicting significant added injury. This system can be used to assess, maintain and treat injured donor lungs.