Anti-Inflammatory Treatment and Active Physical Therapy Have Differing Effects on Functional, Mechanical, and Histological Properties in a Rat Model of Post-Traumatic Elbow Contracture.

Simple elbow dislocation occurs at an incidence of 2.9 to 5.21 dislocations per 100,000 person-years, with as many as 62% of these patients experiencing long-term elbow joint contracture, stiffness, and/or pain. Poor outcomes and the need for secondary surgical intervention can often be prevented nonoperatively with early or immediate active mobilization and physical therapy. However, immobilization or limited mobilization may be necessary following trauma, and it is unknown how different periods of immobilization affect pathological changes in elbow joint tissue and how these changes relate to range of motion (ROM). The purpose of this study was to investigate the effects of varying the initiation of free mobilization on elbow ROM and histological features in an animal model of elbow posttraumatic joint contracture. Traumatic elbow dislocation was surgically induced unilaterally in rats. Injured forelimbs were immobilized in bandages for 3, 7, 14, or 21 days; free mobilization was then allowed until 42 days after injury. Post-mortem joint ROM testing and histological analysis were performed. One-way analysis of variance was used to compare ROM data between control and injured groups, and Pearson correlations were performed between ROM parameters and histological outcomes. Longer immobilization periods resulted in greater ROM reductions. The anterior and posterior capsule showed increases in cellularity, fibroblasts, adhesions, fibrosis, and thickness, whereas the measured outcomes in cartilage were mostly unaffected. All measured histological characteristics of the capsule were negatively correlated with ROM, indicating that higher degrees of pathology corresponded with less ROM. Longer immobilization periods resulted in greater ROM reductions, which correlated with worse histological outcomes in the capsule in an animal model of posttraumatic elbow contracture. The subtle differences in the timing of ROM and capsule tissue changes revealed in the present study provide new insight into the distinct timelines of biomechanical changes as well as regional tissue pathology. This study showed that beginning active mobilization 3 days after injury minimized posttraumatic joint contracture, thereby supporting an immediate-motion clinical treatment strategy (when possible). Furthermore, uninjured but pathologically altered periarticular tissues near the injury location may contribute to more severe contracture during longer immobilization periods as the disease state progresses.

Joint inflammation following remobilization is an important factor in the progression of arthrogenic contracture. We evaluated the effects of an anti-inflammatory treatment during the remobilization period of recovery after joint immobilization in rats. Three groups of rats had their right knee joints immobilized for 3weeks using an external fixator at a flexion of 140° to generate flexion contracture. Next, the fixation device was removed, allowing immobilized knees to freely move again for 1 or 7days. These rats were daily injected with either the steroidal anti-inflammatory drug dexamethasone or saline. Untreated knees were used as controls. At 1day of remobilization, gene expression of pro-inflammatory cytokines, interleukin (IL)-1β, and IL-6 were both increased in the posterior joint capsule, while dexamethasone treatment inhibited increase of these markers. Passive extension range of motion (ROM) was measured before and after myotomy of the knee flexors. Restriction of ROM before myotomy mainly represents the myogenic, and ROM after myotomy shows the arthrogenic changes. Joint immobilization reduced ROM both before and after myotomy. Seven days of remobilization improved ROM before but not after myotomy. Arthrogenic contracture progression following remobilization was characterized by fibrotic reactions of hypercellularity, upregulation of collagen genes, and increased type I and III collagen proteins in the posterior joint capsule. Dexamethasone treatment during the remobilization period improved both myogenic and arthrogenic contractures. Furthermore, remobilization-induced fibrotic reactions in the joint capsule were mostly prevented using dexamethasone. Anti-inflammatory treatment during the recovery period may be a potential therapeutic treatment for joint contracture.

Background:Posttraumatic joint contracture is a debilitating complication following an acute fracture or intra-articular injury that can lead to loss of motion and an inability to complete activities of daily living. In prior studies using an established in vivo model, we found that ketotifen fumarate (KF), a mast cell stabilizer, was associated with a significant reduction in the severity of posttraumatic joint contracture. Our primary research question in the current study was to determine whether a dose-response relationship exists between KF and posttraumatic joint contracture reduction.Methods:A standardized operative method to create posttraumatic joint contracture in a knee was performed on skeletally mature New Zealand White rabbits. The animals were randomly assigned to 1 of 5 groups (n = 10 per group): a nonoperative control group, an operative control group, or 1 of 3 experimental KF groups (0.01 mg/kg [the KF 0.01 group], 0.1 mg/kg [KF 0.1], or 5.0 mg/kg [KF 5.0]). Flexion contractures were measured following 8 weeks of knee immobilization using a hydraulic material-testing machine. The posterior knee joint capsules were then harvested for quantification of myofibroblast and mast cell numbers with immunohistochemistry analysis.Results:Forty-five rabbits were used in the final analysis. Contracture severity was significantly reduced in the KF 0.1 group (p = 0.016) and the KF 5.0 group (p = 0.001) compared with the operative control group. When converted to a percent response, posttraumatic joint contracture reduction was 13%, 45%, and 63% for the KF 0.01, KF 0.1, and KF 5.0 groups, respectively. A half-maximal effective concentration (EC50) for KF of 0.22 mg/kg was established. There was also a decrease in myofibroblasts, mast cells, and substance P-containing nerve fiber counts with increasing doses of KF.Conclusions:Using a preclinical, rabbit in vivo model of posttraumatic joint contracture, increasing doses of KF were associated with decreasing biomechanical estimates of knee posttraumatic joint contracture as well as decreasing numbers of myofibroblasts, mast cells, and substance P-containing nerve fibers.Clinical Relevance:KF has been used safely in humans for more than 40 years and, to our knowledge, is the first and only agent ready to be potentially translated into an effective treatment for posttraumatic joint contracture.

BackgroundIn a majority of cases, whiplash injuries are a domain of conservative therapy. Nevertheless it remains unclear whether physical therapy is of medical or economic benefit in patients with whiplash injuries.MethodsSeventy patients with acute Quebec Task Force (QTF) grade II whiplash injuries were randomized to two therapy groups and received either active (APT) or passive (PPT) physical therapy. Patients were compared with regard to pain and range of motion with data obtained in an earlier study from a group with grade II whiplash injuries in which the therapy recommendation had been "act as usual" (AAU; n = 20). The above-mentioned parameters were assessed at 24 hours and two months after the injury. Furthermore patients' period of disability was documented after two months.ResultsAfter two months, patients in both the APT and PPT groups showed significant improvement in the median period of disability (active: 14 days; passive: 14 days) compared to the AAU group (49 days). No group difference was observed with regard to median improvement in range of motion (active: 120°; passive: 108°; activity as usual: 70°). The median pain reduction was significantly greater in the APT group (50.5) than in the PPT (39.2) or AAU group (28.8).ConclusionOur data show that active physical therapy results in enhanced pain reduction and shortening of post-injury disability. Therefore, active physical therapy should be considered the treatment of choice in patients with QTF grade II whiplash injuries.Trial registrationThe study complied with applicable German law and with the principles of the Helsinki Declaration and was approved by the institutional ethics commission.

Persistent motion loss after free joint mobilization in a rat model of post-traumatic elbow contracture

Background: Post-traumatic joint contracture (PTJC) exhibits distinctive features such as excessive collagen deposition, which is the primary cause of joint capsule fibrosis. This work aimed to examine the therapeutic impacts and the fundamental mechanisms of low-intensity pulsed ultrasound (LIPUS) on PTJC-induced fibrosis, focusing on ferroptosis-related pathways. Methods:RNA sequencing (RNA-seq) data from the Gene Expression Omnibus (GEO) database were analyzed to identify differentially expressed genes (DEGs), followed by enrichment and correlation analyses. 40 Sprague-Dawley rats were separated into 5 groups: Sham, PTJC, Natural, LIPUS, and Combined. Rats in the LIPUS and Combined groups received LIPUS stimulation, while the Combined group also received erastin injections. Hematoxylin and Eosin (H&E) staining quantified inflammatory cell infiltration; Masson’s trichrome staining measured collagen deposition. Immunofluorescence detected Cyclin D1 (fibroblast proliferation), phosphorylated nuclear factor kappa B (p-NF-κB) p65 (inflammation), solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) (ferroptosis markers). Western blotting analyzed Collagen I/III, transforming growth factor beta 1 (TGF-β1)/Smad (fibrosis pathway). Range of motion (ROM) and joint diameter measurements evaluated contracture severity.Results:Bioinformatics analysis identified 17 ferroptosis-related and fibrosis-related target genes, withSLC7A11andGPX4selected for validation. ROM results indicated that LIPUS improved joint contracture more than the PTJC group, but the Combined group had less improvement than the LIPUS group alone. H&E and Masson’s Trichrome staining partially reversing PTJC-induced inflammation and collagen deposition. Mechanistically, immunofluorescence and Western blot indicated that LIPUS reduced fibrosis by decreasing the proliferation-related (Cyclin D1) and inflammation-related protein (p-NF-κB p65), and LIPUS inhibited PTJC-mediated initiation of TGF-β1/Smad signalling pathway and prevented inactivation of theSLC7A11/GPX4axis. Erastin counteracted LIPUS effects, confirming ferroptosis involvement.Conclusions:These findings demonstrate that LIPUS significantly mitigates PTJC-induced joint capsule fibrosis by dual mechanisms: (1) activating theSLC7A11/GPX4axis to inhibit ferroptosis and (2) suppressing TGF-β1/Smad signaling. Ferroptosis-related factors were critical as their inhibition (via erastin) exacerbated fibrosis, highlighting their role in PTJC pathogenesis.

Background/Aims: This study aims to evaluate potential safety events and vital sign changes during active mobilization physical therapy (PT) in critically ill patients undergoing continuous renal replacement therapy (CRRT). Methods: A retrospective review was performed on 29 patients who were treated with CRRT and who underwent 81 PT sessions in a medical intensive care unit at a single referral hospital; 15 patients underwent 33 sessions with passive range of motion (PROM) and 17 patients underwent 48 active mobilization PT sessions. Three patients received both types of PT including 8 PROM and 5 active mobilization PT sessions. The occurrences of safety events and vital sign changes during active mobilization PT sessions were evaluated. Results: The safety events did not develop during 33 sessions with PROM. However, there were 2 safety events (4.1%) during 48 active mobilization PT sessions including one session with mobilization in the bed and the other in a sitting position on the edge of the bed. These safety events exclusively developed during active mobilization PT sessions, in which concomitant extracorporeal membrane oxygenation (ECMO) support and CRRT were delivered. Regarding vital sign changes during PT sessions, there were no significant differences in systolic blood pressure (BP), diastolic BP, mean arterial pressure, heart rate, respiratory rate, or peripheral oxygen saturation before and after both PROM and active mobilization PT sessions. Conclusions: This study showed that active mobilization PT can be performed safely in patients who are being treated with CRRT without a significant hemodynamic change. However, the development of potential safety events in patients with ECMO needs to be monitored carefully.

Post-traumatic joint contracture (PTJC) is a debilitating condition, particularly in the elbow. Previously, we established an animal model of elbow PTJC quantifying passive post-mortem joint mechanics and histological changes temporally. These results showed persistent motion loss similar to what is experienced in humans. Functional assessment of PTJC in our model was not previously considered; however, these measures would provide a clinically relevant measure and would further validate our model by demonstrating persistently altered joint function. To this end, a custom bilateral grip strength device was developed, and a recently established open-source gait analysis system was used to quantify forelimb function in our unilateral injury model. In vivo joint function was shown to be altered long-term and never fully recover. Specifically, forelimb strength in the injured limbs showed persistent deficits at all time points; additionally, gait patterns remained imbalanced and asymmetric throughout the study (although a few gait parameters did return to near normal levels). A quantitative understanding of these longitudinal, functional disabilities further strengthens the clinical relevance of our rat PTJC model enabling assessment of the effectiveness of future interventions aimed at reducing or preventing PTJC.

Objective To observe the differences in functional recovery between active physiother-apy (AP) and continuous passive motion (CPM) after total knee arthroplasty (TKA). Methods Eighty cases of TKA patients were randomly divided into 2 even groups of CPM and AP. In the CPM group, CPM devices were applied in the early days postoperatively; in the AP group, active exercise was encouraged under guidance of rehabilitation physicians. The visual pain scores (VAS) at the 3, 6, 9 days after operation, ranges of motion (ROM) at different time points, and duration of hospitalization were documented for each patient. Results At the third day after operation, CPM group got less VAS than AP group (P 0.05). The follow-ups of 56 patients at 3 and 6 months after operation revealed that the average ROM of AP group was significantly greater than that of CPM group (P < 0.05). Conclusions AP rather than CPM should be recommended in the rehabilitation for patients after TKA. But CPM can be considered for patients with hyperalgesia or those who are unable to take active exercise to accelerate functional recovery. Key words: Motion therapy, continuous passive; Arthroplasty, replacement, knee; Rehabilitation

Purpose/Aim Post-traumatic joint contracture (PTJC) commonly occurs after elbow injury. Previous findings implied immune system activation in capsules of contracted joints; however, quantifying immune cell populations in rodent joint tissues is challenging due to small size and low cellularity. Here, we used flow cytometry to investigate the temporal immune response and enumerate cell populations in the rat elbow capsule after traumatic injury. Materials and Methods After inducing PTJC, capsules were harvested from injured, sham, and control rat elbows at multiple time points, stained with surface markers for immune cells, and quantified via flow cytometry. Results were compared to previously published mechanics and histology data from the same model. Another injured group was treated with celecoxib to determine if changes due to anti-inflammatory treatment could be detected. Results Compared to control, injured animals displayed elevated leukocytes, T cells, and natural killer cells. CD45+ cells exhibited similar temporal changes as mechanics, which increased and then decreased after injury. CD3+, CD4+, and CD8a+ T cells followed a similar pattern as histology scores, which increased and remained elevated. Treating injured animals with celecoxib increased leukocytes but decreased several immune subpopulations. Conclusions A method for flow cytometry on rat elbow capsule was established and used to quantify immune cell populations, which changed in response to injury and anti-inflammatory treatment. Comparisons between flow cytometry and previously published mechanics and histology revealed additional insights about temporal patterns in cell-, tissue-, and joint-level changes. Future work will investigate whether changes in immune cells attenuate PTJC symptoms.

Background: Neurorehabilitation plays a pivotal role in improving functional outcomes for individuals with neurological impairments. Physiotherapy, encompassing both active and passive approaches, is a cornerstone of neurorehabilitation. Understanding the ef𿿿cacy and applications of thesemodalities is crucial for optimizing patient recovery. Aim: This narrative review aims to explore the ef𿿿cacy and clinical applications of active and passive physiotherapy techniques in the rehabilitation of patients with neurological conditions such as stroke, traumatic brain injury, and spinal cord injury. Objective: To analyze and synthesize current literature on the outcomes, bene𿿿ts, and limitations of active and passive physiotherapy techniques, discussing their integration into clinical practice for enhanced rehabilitation outcomes. Methods and Materials: A comprehensive review of published literature was conducted, focusing on studies evaluating active and passive physiotherapy interventions in neurorehabilitation. Relevant articles were sourced from databases such as PubMed, Scopus, and Google Scholar. The review included randomized controlled trials, cohort studies, and systematic reviews that examined the effects of these physiotherapy approaches on functional recovery, neuroplasticity, spasticity management, and patient independence. Results: Active physiotherapy, characterized by patient-driven movements, was found to promote strength, motor control, and functional independence by enhancing neuroplasticity. Passive physiotherapy, which involves external assistance, was bene𿿿cial in preventing joint contractures, reducingspasticity, and maintaining range of motion. Evidence suggests that a combination of both approaches leads to better rehabilitation outcomes, accelerating recovery and improving overall quality of life. Conclusion: Both active and passive physiotherapy techniques hold distinct yet complementary roles in neurorehabilitation. Active physiotherapy fosters neuroplasticity and functional recovery, while passive interventions provide essential support for maintaining mobility and reducing secondary complications. A tailored, patient-speci𿿿c approach integrating both modalities enhancesrehabilitation ef𿿿cacy. Future research should focus on exploring the long-termeffects of combined therapies on neuroplasticity and patient quality of life.

Among older adults, it is not clear how different types or amounts of physical therapy may be associated with improvements in back pain and function. The study objective was to investigate the association between types or amounts of physical therapist services and 1-year outcomes among older adults with back pain. This was a prospective cohort study. A total of 3,771 older adults who were enrolled in a cohort study and who had a new primary care visit for back pain participated. Physical therapy use was ascertained from electronic health records. The following patient-reported outcomes were collected over 12 months: back-related disability (Roland-Morris Disability Questionnaire) and back and leg pain intensity (11-point numerical rating scale). Marginal structural models were used to estimate average effects of different amounts of physical therapy use on disability and pain for all types of physical therapy and for active, passive, and manual physical therapy. A total of 1,285 participants (34.1%) received some physical therapy. There was no statistically significant gradient in relationships between physical therapy use and back-related disability score. The use of passive or manual therapy was not consistently associated with pain outcomes. Higher amounts of active physical therapy were associated with decreased back and leg pain and increased odds of clinically meaningful improvements in back and leg pain relative to results obtained with no active physical therapy. The fact that few participants had high amounts of physical therapy use limited precision and the ability to test for nonlinear relationships for the amount of use. Higher amounts of active physical therapy were most consistently related to the greatest improvements in pain intensity; however, as with all observational studies, the results must be interpreted with caution.

Effects of different low-intensity pulsed ultrasound intensities and durations on a posttraumatic knee joint contracture model in rats

Active physical therapy does not improve outcomes after reverse total shoulder arthroplasty: a multi-center, randomized clinical trial.

Post-traumatic joint contracture induced by scar tissues following a surgery or injury can leave patients in a permanent state of pain and disability, which is difficult to resolve by current treatments. This randomized controlled trial examines the therapeutic effect of pulsed high-intensity laser (PHIL) and pulsed high-intensity focused ultrasound (PHIFU) for post-traumatic joint contracture due to arthrofibrosis. The peak power levels of both PHIL and PHIFU are much higher than that of laser or ultrasound currently used in physical therapy, while short pulses are utilized to prevent damage. To test the effectiveness of these treatments, a rabbit knee model for joint contracture was established. Twenty-one rabbits were split into four groups: untreated control (n = 5), PHIL (n = 5), PHIFU (n = 5), and a PHIL + PHIFU group (n = 6). Maximum extension of the surgically modified rabbit knee was compared to that of the contralateral control knee over the course of 16 weeks. The rabbits in the untreated control group maintained a relatively consistent level of joint contracture, while every rabbit in each of the treatment groups had improved range of motion, eventually leading to a restoration of normal joint extension. Average recovery time was 7.6 ± 1.5 weeks for the PHIL treatment group, 9.8 ± 3.7 weeks for the PHIFU group, and 8.0 ± 2.2 weeks for the combined treatment group. Histopathology demonstrated reduced density and accelerated resorption of scar tissues in the treated knee joints. This study provides evidence that both PHIL and PHIFU are effective in treating post-traumatic joint contracture in rabbits and warrant further investigation into the underlying mechanisms to optimize PHIL and PHIFU based treatments in a larger number of animals.