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Background: Arthrofibrosis is a fibrotic joint disorder resulting in restricted joint motion and pain. Risk factors associated with the development of postoperative arthrofibrosis include female sex, type of graft, and quicker time to reconstruction. These patients have typically benefitted from manipulation under anesthesia or arthroscopic lysis of adhesions. The purpose of this study was to retrospectively review the rate of arthrofibrosis in children and adolescents who previously underwent anterior cruciate ligament (ACL) reconstruction., Materials and Methods: This was a retrospective chart review examining patients 18 years or younger who underwent ACL reconstruction between 2013 and 2023. Data collected included age, body mass index, reconstruction technique, concomitant meniscal or ligamentous pathology, and need for revision surgery for arthroscopic lysis of adhesions vs manipulation under anesthesia., Results: A total of 461 patients 18 years or younger who underwent ACL reconstruction were included in this study. Eighteen (3.90%) patients required reoperation for the development of arthrofibrosis. Skeletally immature patients were found to have a statistically significant lower rate of arthrofibrosis compared with skeletally mature patients (0% vs 4.80%; P =.0184). Patients with a higher weight and body mass index had an increased rate of arthrofibrosis ( P =.0485 and P =.0410, respectively). Graft type did not have a significant impact on arthrofibrosis rates. There were no significant findings in terms of concomitant injuries and rate of arthrofibrosis., Conclusion: Arthrofibrosis developed in 3.90% of patients after ACL reconstruction. Skeletal immaturity may be protective against the development of arthrofibrosis. No association was found between graft type or concomitant knee pathology and arthrofibrosis. [ Orthopedics . 2024;47(4):e161-e166.].

Aims: Neither the long-term development of ablation lesions nor the capability of late gadolinium enhancement (LGE)-MRI to detect ablation-induced fibrosis at late stages of scar formation have been defined. We sought to assess the development of atrial ablation lesions over time using LGE-MRI and invasive electroanatomical mapping (EAM)., Methods and Results: Ablation lesions and total atrial fibrosis were assessed in serial LGE-MRI scans 3 months and >12 months post pulmonary vein (PV) isolation. High-density EAM performed in subsequent repeat ablation procedures served as a reference. Serial LGE-MRI of 22 patients were analyzed retrospectively. The PV encircling ablation lines displayed an average LGE, indicative of ablation-induced fibrosis, of 91.7% ± 7.0% of the circumference at 3 months, but only 62.8% ± 25.0% at a median of 28 months post ablation (p < 0.0001). EAM performed in 18 patients undergoing a subsequent repeat procedure revealed that the consistent decrease in LGE over time was owed to a reduced detectability of ablation-induced fibrosis by LGE-MRI at time-points > 12 months post ablation. Accordingly, the agreement with EAM regarding detection of ablation-induced fibrosis and functional gaps was good for the LGE-MRI at 3 months (κ .74; p < .0001), but only weak for the LGE-MRI at 28 months post-ablation (κ .29; p < .0001)., Conclusion: While non-invasive lesion assessment with LGE-MRI 3 months post ablation provides accurate guidance for future redo-procedures, detectability of atrial ablation lesions appears to decrease over time. Thus, it should be considered to perform LGE-MRI 3 months post-ablation rather than at later time-points > 12 months post ablation, like for example, prior to a planned redo-ablation procedure., (© 2021 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

Background/aim: This study’s aim was to investigate the effects of thymoquinone, which is the essential bioactive component of the volatile oil of Nigella sativa on the peridural fibrosis in rats following laminectomy., Materials and Methods: Twenty female Wistar Albino rats were used in our study. The rats were randomly divided into 2 groups: Sham and Surgery + Thymoquinone. Both groups underwent laminectomy at L1 under general anesthesia. The Sham group was not subjected to any drug application. The 2nd group was treated with intraperitoneal 10-mg/kg thymoquinone once per day for a period of 28 days, following the same surgical procedure. All of the group specimens were sacrificed after 4 weeks, and the laminectomy area was examined in terms of new bone volume, capillary volume, and fibrosis volume using stereological approaches., Results: Statistically significant differences were found between the Sham and Surgery + Thymoquinone groups in terms of new bone volume (P = 0.01), capillary volume (P = 0.01), and fibrosis volume (P < 0.001). It was noted that Thymoquinone caused a significant increase in new bone volume, vascular volume and, a significant decrease in fibrosis volume., Conclusion: The results of our study indicate that thymoquinone is effective in decreasing peridural fibrosis when applied to a laminectomy model., Competing Interests: The authors declare no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Objectives: This study aims to investigate the effect of radial extracorporeal shock wave therapy (rESWT) treatment in the prevention of epidural fibrosis after laminectomy in rats., Materials and Methods: Eighteen 16-month-old male Sprague-Dawley rats weighing 300 g were used in this experimental study between November 2019 and February 2020. The rats were randomly divided into two groups as the control group (L3-L4 total laminectomy without any treatment) and the study group (L3-L4 total laminectomy plus rESWT). The rats were sacrificed at the postoperative sixth week and the lumbar spine was excised en bloc, fixed, and decalcified. Sections were stained with hematoxylin-eosin to evaluate epidural fibrosis, acute inflammation, chronic inflammation, and vascular proliferation., Results: The median value and standard deviations were obtained based on histological examinations. Accordingly, epidural fibrosis decreased significantly in the study group compared to the control group. There was no statistically significant difference between the groups in terms of acute and chronic inflammation response and vascular proliferation., Conclusion: The rESWT application immediately after surgery is effective in preventing epidural fibrosis after laminectomy in rats.

This review details the current understanding of the mechanism of action and corneal effects of mitomycin C (MMC) for prophylactic prevention of stromal fibrosis after photorefractive keratectomy (PRK), and includes discussion of available information on dosage and exposure time recommended for MMC during PRK. MMC is an alkylating agent, with DNA-crosslinking activity, that inhibits DNA replication and cellular proliferation. It acts as a pro-drug and requires reduction in the tissue to be converted to an active agent capable of DNA alkylation. Although MMC augments the early keratocyte apoptosis wave in the anterior corneal stroma, its most important effect responsible for inhibition of fibrosis in surface ablation procedures such as PRK is via the inhibition of mitosis of myofibroblast precursor cells during the first few weeks after PRK. MMC use is especially useful when treating eyes with higher levels of myopia (≥approximately 6 D), which have shown higher risk of developing fibrosis (also clinically termed late haze). Studies have supported the use of MMC at a concentration of 0.02%, rather than lower doses (such as 0.01% or 0.002%), for optimal reduction of fibrosis after PRK. Exposure times for 0.02% MMC longer than 40 s may be beneficial for moderate to high myopia (≥6D), but shorter exposures times appear to be equally effective for lower levels of myopia. Although MMC treatment may also be beneficial in preventing fibrosis after PRK treatments for hyperopia and astigmatism, more studies are needed. Thus, despite the clinical use of MMC after PRK for nearly twenty years-with limited evidence of harmful effects in the cornea-many decades of experience will be needed to exclude late long-term effects that could be noted after MMC treatment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Survival time of kidney transplant patients is primarily threatened by chronic allograft dysfunction (CAD), whose typical feature is interstitial fibrosis and tubular atrophy (IF/TA). CAD could be caused by ischemia-reperfusion injury (IRI) during renal transplantation. MiR-378 is correlated with multiple kidney diseases and implicated in CAD. To clarify the underlying mechanism of miR-378 on renal allograft, we utilize renal unilateral IRI mice and H/R NRK52E cells. To evaluate the acute tubular damage, we determined the apoptotic rate by TUNEL assay and examined mice kidney sections of H&E staining 1 day after IRI. To assess the chronic renal interstitial inflammation and fibrosis, we detected the infiltration rates of CD45R + leukocytes and Ly6b + neutrophils by immunohistochemistry, examined mice kidney sections of picrosirius staining and measured the mRNA level of Col1a1 14 days after IRI. To investigate the H/R injury of NRK52E cells, MTT assay was performed to detect cell viability, TUNEL assay was performed to determine apoptotic rate and luciferase reporter assay was carried out to demonstrate the potential target of miR-378. Moreover, we determined the levels of miR-378 of renal allograft biopsies in healthy patients and patients diagnosed with IF/TA. We found agomir-378 treatment significantly reduced the apoptotic rate and tubular damage scores assessed by H&E staining 1 day after IRI. Agomir-378 treatment also decreased infiltration rates of both CD45R + leukocytes and Ly6b + neutrophils and fibrosis examined by picrosirius staining and by the mRNA level of Col1a1 14 days after IRI. Experiments in vitro revealed that miR-378 increased cell viability and decreased apoptotic rate of NRK52E cells subjected to H/R. Additionally, luciferase reporter assay confirmed that caspase 3 was targeted by miR-378 directly. Furthermore, we found the levels of miR-378 were significantly lower in renal allografts of patients with IF/TA than those of healthy controls. Taken together, we have found that miR-378 has potential protective effects on renal allografts to prevent IRI during kidney transplantation and following IF/TA of renal allografts.

Study Design: Case report., Background: The purpose of this case report is to describe the use of tibiofemoral joint mobilizations to improve knee flexion in a patient with arthrofibrosis following total knee arthroplasty (TKA) and failed manipulation under anesthesia (MUA)., Case Description: A 62-year-old female presented to physical therapy 15 days after TKA with full knee extension, 45 deg of active knee flexion, 48 deg of passive knee flexion, pain, and a Lower Extremity Functional Scale (LEFS) score of 28., Interventions/outcomes: A multimodal intervention strategy was used initially with minimal improvement in knee flexion. The patient was diagnosed with fibrosis and MUA was performed. Passive knee flexion was 80 deg before MUA and 75 deg after MUA. Focused grade III and IV tibiofemoral joint mobilizations were used after MUA. At discharge, the patient had 90 deg of active and 116 deg of passive knee flexion, no pain, and an LEFS score of 80., Discussion: A conventional multimodal intervention approach was ineffective for a patient who developed arthrofibrosis following TKA. A focused intervention approach of grade III and IV tibiofemoral joint mobilizations improved knee flexion, pain, and function following TKA and failed MUA.

Background and Aim: Esophageal stricture is a major complication of large areas endoscopic submucosal dissection (ESD). Until now, the critical mechanism of esophageal stricture remains unclear. We examined the role of mucosal loss versus submucosal damage in esophageal stricture formation after mucosal resection using a porcine model., Materials and Methods: Twelve swine were randomly divided into two groups, each of 6. In each group, two 5-cm-long submucosal tunnels were made to involve 1/3rd of the widths of the anterior and posterior esophageal circumference. The entire mucosal roofs of both tunnels were resected in group A. In group B, the tunnel roof mucosa was incised longitudinally along the length of the tunnel, but without excision of any mucosa. Stricture formation was evaluated by endoscopy after 1, 2, and 4 weeks, respectively. Anatomical and histological examinations were performed after euthanasia., Results: Healing observed on endoscopy in both groups after 1 week. Group A (mucosa resected) developed mild-to-severe esophageal stricture, dysphagia, and weight loss. In contrast, no esophageal stricture was evident in group B (mucosa incisions without resection) after 2 and 4 weeks, respectively. Macroscopic examination showed severe esophageal stricture and shortening of esophagus in only group A. Inflammation and fibrous hyperplasia of the submucosal layer was observed on histological examination in both groups., Conclusion: The extent of loss of esophageal mucosa appears to be a critical factor for esophageal stricture. Inflammation followed by fibrosis may contribute to alteration in compliance of the esophagus but is not the main mechanism of postresection stricture.

Background: Cyclops syndrome after anterior cruciate ligament (ACL) reconstruction is due to a fibrous nodule that develops in the anterior part of the intercondylar notch and prevents full knee extension. The primary objective of this systematic literature review was to evaluate the incidence of symptomatic cyclops lesion after ACL reconstruction. The secondary objective was to identify risk factors for cyclops syndrome., Hypothesis: Cyclops syndrome is common after ACL reconstruction and has several risk factors reported in the literature., Methods: A systematic literature review was performed by searching the PubMed, Medline, CINAHL, Cochrane, and Embase databases with the key terms 'cyclops' and 'ACL reconstruction'. The data thus retrieved were evaluated independently by two investigators. All articles in English or French that reported the incidence and risk factors of cyclops syndrome after ACL reconstruction were included., Results: The search retrieved the titles and abstracts of 79 articles, of which 20 were selected to be read in full; among these, 10 were included in the study. The incidence of symptomatic cyclops lesion ranged from 1.9% to 10.9%. Identified risk factors were as follows: pre-operatively, knee inflammation and/or motion restriction at the time of ACL reconstruction; intra-operatively, narrow intercondylar notch and excessively anterior position of the tibial tunnel; and post-operatively, persistent hamstring muscle spasm., Discussion: Development of a cyclops lesion is common after ACL reconstruction, occurs early, and may require further surgery. The knowledge of the risk factors provided by this study may improve the ability to devise effective preventive measures., Level of Evidence: II, systematic literature review., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Arthrofibrosis can be a devastating complication after ligamentous knee reconstruction. Beyond early range of motion (ROM), manipulation under anesthesia (MUA) and arthroscopic lysis of adhesions (LOAs) are the most frequently employed interventions for the condition. There is a paucity of data regarding predictive factors of arthrofibrosis requiring MUA and LOA, and even less data regarding changes in validated patient-reported outcome measures following the procedure. A retrospective case-control study was performed at an academic, urban Level I trauma center of patients that developed arthrofibrosis requiring MUA and LOA following ligamentous reconstruction. The indication for LOA was failure to achieve a 90° arc of ROM by 6 weeks. Seventeen cases and 141 controls were identified. Follow-up for cases was 26.9 ± 17.1 months (mean ± standard deviation). Time from initial reconstruction to LOA was 75.2 ± 27.9 days. Cases had higher body mass indices by a mean of 2.9 ( p  = 0.024). The most significant risk factors for stiffness were concomitant anterior cruciate ligament, posterior cruciate ligament, and posterolateral corner/lateral collateral ligament injury (odds ratio [OR], 17.08), knee dislocation (OR, 12.84), and use of an external fixator (OR, 12.81, 95% confidence interval [CI], 3.03-54.20) (all p  < 0.0026). Mean Knee Injury and Osteoarthritis Outcome Scores, Western Ontario and McMaster Universities Osteoarthritis Indices, and International Knee Documentation Committee scores improved by 47.5, 50.5, and 47.3% (all p  < 0.0038), respectively. All patients reported improvement in pain, with maximum daily pain scores improving by a mean of 4.1 points on the Numeric Pain Rating Scale ( p  < 0.001). Mean ROM arc improved by 38.8° ( p  < 0.001). All 17 cases were satisfied with the procedure. Twelve cases (70.59%) reported a full return to preinjury level of activity. No factors were identified that predicted success from the procedure, likely due to inadequate sample size. Arthrofibrosis following knee injury and ligamentous reconstruction can be predicted by the severity of injury and early intervention with MUA and arthroscopic LOA can lead to a satisfactory outcome for the patient., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Introduction: We evaluated the prognostic role of the arterial oxygen partial pressure/fractional inspired oxygen ratio (PaO 2 /FiO 2 ratio) measured at the end of double-lung transplantation (DLT)., Methods: This was a monocentric cohort study of all consecutive DLT patients between January 1, 2012, and January 1, 2016, except patients with preoperative extracorporeal membrane oxygenation (ECMO), intraoperative cardiopulmonary bypass, postoperative ECMO, large patent foramen ovale, redo transplantation during the study period, and multiorgan transplantation., Results: A total of 164 patients were included in the study; 45 had a PaO 2 /FiO 2 ratio <200, 39 a ratio in the range 200-300, and 80 a ratio >300. The risk of being in the lower ratio group is positively related to body mass index, preoperative pulmonary hypertension, and fibrosis. It is negatively related to emergency surgery, age, and intraoperative institution of ECMO. There was a trend for more grade 3 pulmonary graft dysfunction at day 3 in the worst PaO 2 /FiO 2 ratio group. Mortality at 1000 days was similar for all patients and even after exclusion of patients who had required intraoperative ECMO., Conclusion: PaO 2 /FiO 2 ratio measured at the end of DLT does not forecast 1000-day mortality., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: Risk factors for stiffness after arthroscopic rotator cuff repair (RCR) have been limited to studies with small patient numbers. The objective is to determine patient-related risk factors for stiffness after RCR., Methods: The PearlDiver database was queried from 2007 to 2015 for patients undergoing isolated arthroscopic RCR. A multivariate binomial logistic regression analysis assessed for risk factors requiring a postoperative manipulation under anesthesia (MUA) or lysis of adhesions (LOA) within 9 months after RCR., Results: Two hundred thirty-two of 19,229 patients (1.2%) underwent a LOA and/or MUA within 9 months after arthroscopic RCR. Significant risk factors identified were age less than 50 years (odds ratio [OR], 1.9; P < 0.0001), female gender (OR, 2.0; P < 0.0001), diabetes mellitus (DM) type I (OR, 2.7; P < 0.0001), hypothyroidism (OR, 1.3; P = 0.020), and systemic lupus erythematosus (OR, 2.1; P = 0.004). However, tobacco use was associated with a 0.5 risk of developing stiffness (P < 0.0001)., Discussion: Systemic lupus erythematosus, hypothyroidism, and DMI (but not DMII) in addition to young age and female gender were risk factors for LOA/MUA after arthroscopic RCR.

Introduction: Atlanto-axial rotatory fixation (AARF) is a rare complication of ventriculo-peritoneal shunt (VPS) surgery., Case Presentation: The authors present a unique case of AARF developing early after VP shunting, with persistent torticollis, a "cock-robin" head position, and a thick fibrous band along the catheter path. Due to refractoriness to conservative treatments, AARF, which can be an early-onset complication of VPS surgery, was resolved by removing the distal catheter along with the fibrous band encasing it., Conclusion: Surgical removal of the fibrous band might be enough to solve such complication with no need of further surgical fusion procedures.

Aim: To investigate the effects of local and systemic administration of methyl palmitate on the formation of epidural fibrosis., Material and Methods: Twenty-eight rats were randomly divided into four equal groups (control, Spongostan, local methyl palmitate and orally methyl palmitate) and laminectomy was performed between T11 and L1 in all rats. Local methyl palmitate (300 mg/kg) was applied with Spongostan; methyl palmitate (300 mg/kg) was given orally three times per week on different days for a total period of 4 weeks. Four weeks later, the vertebral column from T9 to L3, including the paraspinal muscles and epidural scar tissue, was removed en bloc and epidural fibrosis and arachnoidal involvement was graded and evaluated histopathologically. Kruskal-Wallis and Pearson Chi-Square test were used for statistical analysis. A statistically significant p-value was determined as p < 0.05., Results: The grading of epidural fibrosis was lower at a statistically significant level in orally-administrated methyl palmitate groups compared to the control and spongostan groups (p < 0.05)., Conclusion: The findings of this study show that oral methyl palmitate decreases the formation of epidural fibrosis and that this effect of methyl palmitate could be mediated by reducing the functions of inflammatory cells such as macrophages, neutrophils and fibroblasts, including anti-inflammatory and antioxidant effects.

Objectives: What patient characteristics and injury factors predict decreased knee range of motion (ROM) after operative management of tibial plateau fractures?, Design: Prospective cohort study., Setting: Academic medical center., Patients: Over 11 years, tibial plateau fractures at a single academic institution were prospectively followed. A total of 266 patients were included in this study., Intervention: Surgical repair of tibial plateau fractures and secondary interventions due to arthrofibrosis., Main Outcome Measure: Clinical outcomes were evaluated using the Short Musculoskeletal Function Assessment and ROM at 3-month, 6-month, and long-term follow-up. Secondary outcomes were considered as the need for a subsequent procedure due to arthrofibrosis., Results: At 3-month follow-up, the mean ROM was 113 degrees. By long-term follow-up (mean = 17 months), the mean ROM improved to 125 degrees. Independent predictors of decreased knee ROM were the following: at 3-month follow-up, open fractures (P = 0.047), application of a knee-spanning external fixator (P = 0.026), orthopaedic polytrauma (P = 0.003), and tibial spine involvement (P = 0.043); and at long-term follow-up, nonwhite ethnicity (P = 0.003), increasing age (P = 0.003), and a deep infection (P = 0.002). Ten patients (3.7%) required a secondary procedure for arthrofibrosis. There was a significant improvement in the knee ROM (P < 0.001) and functional outcomes (P = 0.004) following the intervention., Conclusions: At long-term follow-up, independent predictors of decreased knee ROM were nonwhite ethnicity, increasing age, and sustaining a postoperative complication of a deep infection. Secondary interventions were reliable treatments for arthrofibrosis., Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Purpose: To compare the effect of different laser pulse energy settings in femtosecond laser-assisted cataract surgery with that of standard phacoemulsification and no energy at all used on posterior capsule opacification (PCO) in vitro., Setting: Cell and Molecular Biology Research Laboratory, Department of Ophthalmology, Ludwig-Maximilians-University Munich, Real Eyes, Ophthalmology Center, Munich, and Institute for Clinical Pathology, Goethe University Frankfurt, Frankfurt, Germany., Design: Experimental study., Methods: Fifteen cadaver capsular bags were cultivated from 8 human donors under standard cell culture conditions. For preparation of the capsular bag, 4 groups were established as follows: femtosecond laser-assisted cataract surgery standard energy (n = 3), femtosecond laser-assisted cataract surgery high energy (n = 3), phacoemulsification (n = 6), and hydrodissection without energy (extracapsular cataract extraction) (n = 3). Growth of lens epithelial cells was observed and photodocumented. The days until full cell coverage of the posterior capsule were documented. Capsular bags were stained for fibronectin, α-smooth muscle actin, and collagen type 1., Results: Cell growth patterns in all treatment groups were comparable, with no statistically significant differences detected at any timepoint measured (P = .81, Kruskal-Wallis). The markers for fibrosis were equally distributed in all groups, indicating an equal fibrotic reaction in all groups., Conclusion: Femtosecond laser-assisted cataract surgery did not increase different cellular responses in PCO formation comparison with phacoemulsification in vitro, even when higher laser pulse energy levels were used., (Copyright © 2018 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

The treatment of sports injuries in the skeletally immature has a unique set of complications. Growth deformity may occur after anterior cruciate ligament reconstruction; therefore, skeletal age is used to help guide the choice between physeal sparing and transphyseal techniques. Arthrofibrosis after tibial spine fracture fixation can be reduced by initiating immediate range of motion, and should be treated early and cautiously to avoid iatrogenic fracture. Nonunions of medial epicondyle elbow fractures are more common with nonoperative treatment, but seldom lead to clinical problems outside of certain athletes. Risks of OCD fixation are specific to the material of screw used., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Separating wounded serosa by physical barriers is the only clinically approved adjunct for postoperative adhesion prevention. Since the optimal adhesion barrier has not been found, it is essential to improve our pathogenic understanding of adhesion formation and to compare the effects of different barrier materials on tissue and cells. Wistar rats underwent standardized peritoneal damage and were treated either with Seprafilm, Adept, Intercoat, Spraygel, SupraSeal or remained untreated as a control. 14 days postoperatively, the lesions were explanted and histomorphologically analyzed using the European ISO score to evaluate material implants. Striking differences between the material groups were present regarding the inflammation, fibrosis, and foreign body reaction. According to the ISO score, Intercoat and Spraygel were considered as nonirritating to tissue. Adept, Seprafilm, and SupraSeal were assessed as mild-irritating materials. Interestingly, the most effective material in adhesion prevention revealed moderate inflammation accompanied by minor fibrosis. The degree of inflammation to barrier materials does not predict the efficacy in the prevention of adhesions. Histopathological investigations are crucial to improve our understanding of the cellular mechanisms during adhesion formation and elucidate the tissue response to material approaches used in adhesion prevention. This will lead to improved antiadhesive strategies and the development of functional barrier biomaterials. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 598-609, 2018., (© 2017 Wiley Periodicals, Inc.)

Interstitial fibrosis is an important contributor to graft loss in chronic renal allograft injury. Inflammatory macrophages are associated with fibrosis in renal allografts, but how these cells contribute to this damaging response is not clearly understood. Here, we investigated the role of macrophage-to-myofibroblast transition in interstitial fibrosis in human and experimental chronic renal allograft injury. In biopsy specimens from patients with active chronic allograft rejection, we identified cells undergoing macrophage-to-myofibroblast transition by the coexpression of macrophage (CD68) and myofibroblast ( α -smooth muscle actin [ α -SMA]) markers. CD68 + / α -SMA + cells accounted for approximately 50% of the myofibroblast population, and the number of these cells correlated with allograft function and the severity of interstitial fibrosis. Similarly, in C57BL/6J mice with a BALB/c renal allograft, cells coexpressing macrophage markers (CD68 or F4/80) and α -SMA composed a significant population in the interstitium of allografts undergoing chronic rejection. Fate-mapping in Lyz2-Cre/Rosa26-Tomato mice showed that approximately half of α -SMA + myofibroblasts in renal allografts originated from recipient bone marrow-derived macrophages. Knockout of Smad3 protected against interstitial fibrosis in renal allografts and substantially reduced the number of macrophage-to-myofibroblast transition cells. Furthermore, the majority of macrophage-to-myofibroblast transition cells in human and experimental renal allograft rejection coexpressed the M2-type macrophage marker CD206, and this expression was considerably reduced in Smad3 -knockout recipients. In conclusion, our studies indicate that macrophage-to-myofibroblast transition contributes to interstitial fibrosis in chronic renal allograft injury. Moreover, the transition of bone marrow-derived M2-type macrophages to myofibroblasts in the renal allograft is regulated via a Smad3-dependent mechanism., (Copyright © 2017 by the American Society of Nephrology.)

Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV-positive, compared to 443 HCV-negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1-, 3-, and 5-year survival were similar in HCV RNA-positive versus -negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long-term follow-up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon-free HCV therapies this should not be a barrier to LuTx., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Arthrofibrosis following total knee arthroplasty (TKA) is a common problem, which can be frustrating to both the patient and treating physician and can dramatically compromise post-operative function. Current treatment options for TKA arthrofibrosis include watchful waiting, injections, physical therapy, manipulation under anaesthesia, arthroscopic/open lysis of adhesions and revision surgery. We present a novel technique to treat acute and chronic stiffness following TKA, which we call hydraulic distension., Methods: A retrospective pre- and post-operative inpatient and outpatient record review of three patients treated with hydraulic distension for arthrofibrosis following TKA at a single institution., Results: Three patients with a mean age of 74 years (68-78) underwent hydraulic distension of the knee at a mean of 23.4 ± 18.4 months (9 weeks to 36 months) following primary TKA. The mean pre-distension maximum flexion was 86.7 ± 10.4°, and the mean post-distension flexion was 110 ± 13.2° (23.3° increase). The patients maintained a mean 110 ± 20° flexion (23.3° increase) at a mean follow-up of 11.7 months (1 week to 29 months). There were no complications., Conclusion: We present a novel technique for managing arthrofibrosis following TKA that has not been previously reported. This is an effective, safe procedure, with our patients experiencing a mean 23° increased knee flexion at the most recent follow-up., (Published 2016. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Intestinal fibrosis is a common feature of Crohn's disease and may appear as a stricture, stenosis, or intestinal obstruction. Fibrostenosing Crohn's disease leads to a significantly impaired quality of life in affected patients and constitutes a challenging treatment situation. In the absence of specific medical antifibrotic treatment options, endoscopic or surgical therapy approaches with their potential harmful side effects are frequently used. However, our understanding of mechanisms of fibrogenesis in general and specifically intestinal fibrosis has emerged. Progression of fibrosis in the liver, lung, or skin can be halted or even reversed, and possible treatment targets have been identified. In face of this observation and given the fact that fibrotic alterations in various organs of the human body share distinct core characteristics, this article aims to address whether reversibility of intestinal fibrosis may be conceivable and to highlight promising research avenues and therapies.

Background: It is unclear whether the myocardium undergoes accelerated fibrotic remodeling in children after heart transplantation (HTx)., Methods: In this prospective study, cardiac magnetic resonance (CMR) studies in 17 patients 1.3 years (median, range 0.03-12.6 years) after HTx (mean age, 9.8 ± 6.2 years; 8 girls) were compared to CMR studies in 9 healthy controls (mean age, 12.4 ± 2.4 years; 4 girls). T1 measurements were performed at a midventricular short axis slice before (ie, native T1 times) and after the application of 0.2 mmol/kg gadopentetate dimeglumine in the interventricular septum, left ventricular (LV) free wall and encompassing the entire LV myocardium. The tissue-blood partition coefficient (TBPC), reflecting the degree of diffuse myocardial fibrosis, was calculated as a function of the ratio of T1 change of myocardium compared to blood. Native T1 times and TBPC were correlated with echocardiographic parameters of diastolic function., Results: Native T1 times were significantly higher in HTx patients compared to controls in all regions assessed (LV free wall 973 ± 42 vs 923 ± 12 ms; P < 0.005; interventricular septum 1003 ± 31 vs 974 ± 21 ms, P < 0.05; entire LV myocardium 987 ± 33 vs 951 ± 16 ms; P < 0.005) and correlated with LV E/e' as an echocardiographic marker of diastolic dysfunction (r = 0.54, P < 0.05). The TBPC was elevated in the LV free wall (0.45 ± 0.06 vs 0.40 ± 0.03, P < 0.005) and the entire LV myocardium (0.47 ± 0.06 vs 0.43 ± 0.03, P < 0.05)., Conclusions: Evidence of diffuse myocardial fibrosis and is already present in children after HTx. It appears to be associated with diastolic dysfunction.

The aim of this study was to investigate the effects of intracochlear bleeding during cochleostomy on cochlear inflammatory response and residual hearing in a guinea pig animal model. Auditory brainstem response threshold shifts were greater in blood injected ears (p<0.05). Interleukin-1β, interleukin-10, tumor necrosis factor-α and nitric oxide synthase 2, cytokines that are related to early stage inflammation, were significantly increased in blood injected ears compared to normal and cochleostomy only ears at 1 day after surgery; with the increased IL-1β being sustained until 3 days after the surgery (p<0.05). Hair cells were more severely damaged in blood injected ears than in cochleostomy only ears. Histopathologic examination revealed more extensive fibrosis and ossification in blood injected ears than cochleostomy only ears. These results show that intracochlear bleeding enhanced cochlear inflammation resulting in increased fibrosis and ossification in an experimental animal model.

Hip replacements with metal-on-metal components can cause a spectrum of adverse tissue reactions-from benign localized fibrosis and chronic inflammation to delayed hypersensitivity response. In addition to history, physical examination, and relevant laboratory data, imaging plays a critical role in the evaluation of hip arthroplasties. Imaging assessment begins with radiographs and may be followed by ultrasound, computed tomography, or MRI. MRI optimized for metal artifact reduction is the most sensitive and specific imaging modality and is essential in assessing the spectrum of metal-related adverse tissue reactions. In this article, we discuss the history, pathophysiology, and imaging findings of adverse reactions to metal debris., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Non-alcoholic fatty liver disease (NAFLD) affects a substantial proportion of the world population, and its prevalence has been increasing. The study was aimed at evaluating the prevalence and peri-transplant risk factors for post-liver transplantation (LT) NAFLD. A retrospective review was performed for adult recipients who underwent late protocol biopsy (>1 yr after LT) between August 2010 and December 2012. Hepatic steatosis was reviewed and graded by hepatopathologists, and the peri-transplant factors were analyzed for relationships to histologically proven NAFLD. Total 166 biopsies had been performed in 156 recipients. NAFLD was present in 27.1% at a mean period of 35.4 months between LT and biopsy, moderate and severe steatosis (≥33%) consisted of 28.9%. In multivariate analysis, pre-LT alcoholic cirrhosis (odds ratio [OR] 8.031, p = 0.003), obesity at biopsy (OR 3.873, p = 0.001), and preexisting donor graft steatosis (OR 3.147, p = 0.022) were significant risk factors for post-LT NAFLD. In conclusion, NAFLD represented a considerable portion of recipients, but this prevalence was not higher than those for general population. Three risk factors were significantly related to post-LT NAFLD, and recipients with those factors should be monitored for NAFLD. Furthermore, possible progression to non-alcoholic steatohepatitis (NASH) or fibrosis and metabolic syndrome should be considered in future studies., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Progressive anterior segment fibrosis syndrome (ASFS), after intraocular surgery in older children (≥ 9 years) and adults with congenital aniridia, is described in the literature. In this report, we describe an unique case of ASFS in an infant with congenital aniridia following a combined trabeculotomy-ectomy and its recurrence after a descemet stripping endothelial keratoplasty. The ophthalmologists should be well aware of this entity and warn the parents about its possibilities. Use of immunomodulators or prolonged anti-inflammatory therapy may be considered to prevent its occurrence.

Background: Total knee arthroplasty (TKA) and related interventions such as revision TKA and the treatment of infected TKAs are commonly performed procedures. Hospital readmission rates are used to measure hospital performance, but risk factors (both medical and surgical) for readmission after TKA, revision TKA, and treatment for the infected TKA have not been well characterized., Questions/purposes: We measured (1) the unplanned hospital readmission rate in primary TKA and revision TKA, including antibiotic-spacer staged revision TKA to treat infection. We also evaluated (2) the medical and surgical causes of readmission and (3) risk factors associated with unplanned hospital readmission., Methods: This retrospective cohort study included a total of 1408 patients (1032 primary TKAs, 262 revision TKAs, 113 revision of infected TKAs) from one institution. All hospital readmissions within 90 days of discharge were evaluated for timing and cause. Diagnoses at readmission were categorized as surgical or medical. Readmission risk was assessed using a Cox proportional hazards model that incorporated patient demographics and medical comorbidities., Results: The unplanned readmission rate for the entire cohort was 4% at 30 days and 8% at 90 days. At 90 days postoperatively, revision of an infected TKA had the highest readmission rate, followed by revision TKA, with primary TKA having the lowest rate. Approximately three-fourths of readmissions were the result of surgical causes, mostly infection, arthrofibrosis, and cellulitis, whereas the remainder of readmissions were the result of medical causes. Procedure type (primary TKA versus revision TKA or staged treatment for infected TKA), hospital stay more than 5 days, discharge destination, and a fluid/electrolyte abnormality were each associated with risk of unplanned readmission., Conclusions: Patients having revision TKA, whether for infection or other causes, are more likely to have an unplanned readmission to the hospital than are patients having primary TKA. When assessing hospital performance for TKA, it is important to distinguish among these surgical procedures.

Proposed technique provides prevention of formation of anterior lens capsule fibrous ring, capsule deformity and intraocular lens (IOL) dislocation in the late postoperative period when a minor additional intraoperative procedure is performed that is 4-6 penetrating radial incisions 0.5-1.0 mm long starting from capsulorhexis margin before nucleus removal or after IOL implantation into the capsule bag.

ABSTRACT Postoperative adhesion formation following complex strabismus surgery limits surgical outcomes. The benefits of amniotic membrane transplant (AMT) are widely recognized in ophthalmology. There are only published isolated case reports regarding its use in strabismus surgery. The limitation of these reports is that they describe use of AMT in cases of restrictive strabismus resulting from periocular surgery and indirect involvement of the extraocular muscles. In our series, the amniotic membrane was used to manage complex strabismus surgery. In this retrospective case series we describe surgical management with AMT in 8 strabismus cases between 2007 and 2010 in a tertiary referral center. Of these, 6 cases resulted from complex and repeat strabismus procedures to the extraocular muscles and 2 cases were a result of periocular surgery. Descriptive methodology was used. Outcomes examined were postoperative objective improvement in angle of deviation, subjective improvement in patient symptoms, and need for further interventions. Mean follow-up period was 15 months. All patients had multiple strabismus surgery in the past with a mean number of 3.2 ± 1.5 procedures (range 1-5). The indication for surgery using amniotic membrane graft was in 7 cases a large hypotropia with inferior conjunctival fibrosis and in one case a large consecutive horizontal deviation. The mean angle of vertical deviation was reduced from 32.1 ± 13 prism diopters (PD) preoperatively to 19.75 ± 11.4 PD postoperatively, with better outcomes in cases where AMT was used early in the surgical plan. Six out of the eight cases had objective improvement also consistent with improvement in the binocular field of vision. This is the largest reported case series on amniotic membrane grafts for strabismus surgery complicated by fibrosis and especially cases of consecutive hypotropia. Our outcomes indicate that AMT is beneficial, but we suggest it be used in the early stages of the surgical management of these cases.

Fibrosis is a serious condition complicating chronic inflammatory processes affecting the intestinal tract. Advances in this field that rely on human studies have been slow and seriously restricted by practical and logistic reasons. As a consequence, well-characterized animal models of intestinal fibrosis have emerged as logical and essential systems to better define and understand the pathophysiology of fibrosis. In point of fact, animal models allow the execution of mechanistic studies as well as the implementation of clinical trials with novel, pathophysiology-based therapeutic approaches. This review provides an overview of the currently available animal models of intestinal fibrosis, taking into consideration the methods of induction, key characteristics of each model, and underlying mechanisms. Currently available models will be classified into seven categories: spontaneous, gene-targeted, chemical-, immune-, bacteria-, and radiation-induced as well as postoperative fibrosis. Each model will be discussed in regard to its potential to create research opportunities to gain insights into the mechanisms of intestinal fibrosis and stricture formation and assist in the development of effective and specific antifibrotic therapies.

Stereotactic body radiation therapy (SBRT) is a new radiotherapy treatment method that has been applied to the treatment of Stage I lung cancers in medically inoperable patients, with excellent clinical results. SBRT allows the delivery of a very high radiation dose to the target volume, while minimizing the dose to the adjacent normal tissues. As a consequence, CT findings after SBRT have different appearance, geographic extent and progression timeline compared to those following conventional radiation therapy for lung cancer. In particular, SBRT-induced changes are limited to the "shell" of normal tissue outside the tumor and have a complex shape. When SBRT-induced CT changes have a consolidation/mass-like appearance, the differentiation from tumor recurrence can be very difficult. An understanding of SBRT technique as it relates to the development of SBRT-induced lung injury and familiarity with the full spectrum of CT manifestations are important to facilitate diagnosis and management of lung cancer patients treated with this newly emerging radiotherapy method., (Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The aim of the study was to describe the clinical features, histopathological findings, and management of eyes presenting with a thick membrane after anterior stromal puncture (ASP) for bullous keratopathy., Study Design: Retrospective interventional case series., Methods: Retrospective chart analysis of 3 eyes presenting with a thick membrane between 12-30 months after ASP was done. Patients presented with complaints of recurrent symptoms of pain, watering, and irritation. The membrane was peeled off from the corneal surface in the operation room and sent for histopathological evaluation. A cryopreserved amniotic membrane was secured on the corneal surface using 10-0 nylon interrupted sutures., Results: Patients reported alleviation of symptoms after the procedure and remained asymptomatic at the final follow-up (range 6-12 months). Histopathological evaluation of the excised membrane revealed the presence of a hyperplastic epithelium with loose fibrocollagenous tissue suggestive of subepithelial fibrosis., Conclusions: Subepithelial fibrosis after ASP, although a known entity, may rarely present as a thick membrane because of exaggerated response resulting in the recurrence of symptoms. This can be successfully managed by superficial keratectomy and amniotic membrane transplant.

Background: The CryoMaze procedure is usually limited to endocardial ablation under cardio-pulmonary bypass. Epicardial ablation is considered inferior as endocardial islets of atrial tissue could theoretically remain viable, protected from cryoinjury by epicardial fat and endocardial circulating warm blood. Novel argon-powered cryoprobes with lower ablation temperatures have recently become available. It is unclear if these instruments can reliably induce transmural atrial fibrosis by epicardial cryoablation on the beating heart., Methods: Ten sheep were divided into two equal groups. CryoMaze ablations were applied using an argon-powered cryoprobe with an ablation temperature of -185°C. In the control group, standardized ablations (n = 50) were applied endocardially under cardiopulmonary bypass. In the experimental group, corresponding ablations (n = 50) were applied epicardially on the beating heart. Postoperatively the animals were monitored for 30 days. At necropsy, the lesions were explanted and analyzed histologically for evidence of transmural fibrosis., Results: Two animals in the control group and one animal in the experimental group died prematurely. Autopsy of the remaining animals showed that all lesions (n = 70) had retained their structural integrity. In the control group, histology demonstrated transmural fibrosis in 94% (28/30) of the endocardially applied lesions. In the experimental group, histology demonstrated transmural fibrosis in 95% (38/40) of the epicardially applied lesions. Statistical analysis revealed no significant difference between the two groups (p = 0.96)., Conclusion: Argon-powered epicardial cryoablation on the beating heart is as efficient in inducing transmural fibrosis as the traditional technique of endocardial ablation under cardio-pulmonary bypass., (© 2011 Wiley Periodicals, Inc.)

Aim: Postlaminectomy epidural fibrosis is the formation of scar tissue over the dura mater following posterior spinal surgery. This devastating complication is responsible for the substantial amount of failed back syndromes. MATERIAL and, Methods: Twenty male Wistar-Albino rats each weighing 350-400 grams were used. Following L3-L5 laminectomy, the rats were randomly divided into 2 groups, with 10 rats in each group. In the control group, only a laminectomy was performed. In the drug group, 5 mg/ml tacrolimus was topically applied with a cotton pad soaked with the drug solution for 5 minutes. The animals were killed on the 30th postoperative day injecting a lethal dose (250 mg/kg) of pentobarbital and the involved dural segments were removed for histopathological and ultrastructural evaluations., Results: Epidural scar thickness and the density were significantly lower in the animals treated with tacrolimus than those of the control group., Conclusion: Promising evidence regarding the anti-scar potential of tacrolimus merits further research to optimize the dosage and the usage of the drug.

Background: Inflammation and subsequent fibrosis, adhesions, or plicae may limit normal capsular compliance and decrease volume capacity of the knee., Hypothesis: Patients with fibrosis, anterior interval scarring, adhesions, or palpable painful plicae will have decreased knee volumes when compared to controls, and selective arthroscopic releases will restore volume to normal levels., Study Design: Descriptive laboratory study and cohort study; Level of evidence, 2., Methods: In part I, knee volume and pressure were recorded in 14 fresh-frozen human cadaveric knees, and the maximum volume capacity was identified before capsular disruption. In part II, 49 patients undergoing arthroscopy were divided into 2 groups based on intraoperative volume assessment at 50 mm H(2)O pressure: group 1 (n = 20) with normal volume (<1 standard deviation below the mean established in part I) and group 2 (n = 29) knees with deficient volume (>1 standard deviation below mean). Group 2 underwent volume-changing procedures such as lysis of adhesions, anterior interval release, and plica resections, while group 1 underwent volume-neutral procedures including meniscal or chondral surgery. The knee volume was then reassessed after arthroscopy., Results: The average volume capacity of the knees in the cadaveric study was 87.5 ± 21.7 mL (range, 50-120 mL). There was no statistical difference between the presurgical (98.9 ± 29.8 mL) and postsurgical volumes (99.4 ± 29.1 mL) in group 1; P = .65. The presurgical volume in group 2 (46.1 ± 13.0 mL) was significantly lower than group 1 (P = .001). The group 2 volume increased to 78.5 ± 24.2 mL after surgery (P = .001), with an average change in volume of 75.5%. The mean change in volume after surgery was significantly greater in group 2 (32.3 mL) versus group 1 (0.45 mL) (P = .001). At 1-year follow-up, the mean Tegner score in the volume-compromised group 2 increased from 2.0 ± 1.4 preoperatively to 4.0 ± 2.0 postoperatively (P = .01), the Lysholm score increased from 45.0 ± 24.0 preoperatively to 76.8 ± 25.4 postoperatively (P = .003), and the average Short Form-12 quality of life score increased from 32.4 ± 8.7 preoperatively to 45.0 ± 11.0 postoperatively (P = .005)., Conclusions: The average volume of the human knee in this study was between 65 and 110 mL (±1 standard deviation of mean of 87.5 mL). Although patients with chronic knee pain may have pain from multiple sources, some may have diminished knee volume, and selected arthroscopic releases can restore knee volume to near-normal levels.

Purpose: To analyze risk factors for postoperative recurrence of fibrovascular tissue in eyes with aggressive posterior retinopathy of prematurity (AP ROP) treated with early vitreous surgery., Design: Retrospective, consecutive, observational case series., Methods: Thirty-one patients (50 eyes) with AP ROP who underwent early vitreous surgery between March 2005 and April 2008 participated. Eyes with stage 4A or 4B disease in which fibrovascular tissue was not attached to the vitreous base were included; those in which fibrovascular tissue was attached extensively to vitreous base or those without dense photocoagulation to the nonvascularized retina were excluded. Eligible eyes were divided into 2 groups based on postoperative recurrence or no recurrence of fibrovascular tissue. Data on gender, gestational age, birth weight, Apgar score, intubation duration, severe systemic complications, preoperative ROP stage, zone, fibrovascular tissue and vitreous base adhesion, clock hours of fibrovascular tissue, postmenstrual age at the initial application of dense photocoagulation, dense photocoagulation to both vascularized and nonvascularized retina, postmenstrual age at vitrectomy, and intraoperative hemorrhage were collected and analyzed., Results: Fifty eyes of 31 patients underwent early vitrectomy. Seven (14%) eyes were excluded and 43 eyes (86%) were included. Eight (18%) of 43 eyes had a recurrence of fibrovascular tissue. Both univariate and multivariate analysis indicated application of dense photocoagulation to both the vascularized and nonvascularized retina was a significant factor in the decreased recurrence of fibrovascular tissue (P = .002 and P = .008, respectively)., Conclusions: Application of preoperative dense photocoagulation to vascularized and nonvascularized retina may be important for lowering the recurrence of fibrovascular tissue in eyes with AP ROP., (2010 Elsevier Inc. All rights reserved.)

Purpose of Review: Chemoradiation has become a common approach in the treatment of advanced head and neck cancer. Its effectiveness in eradicating associated nodal metastases has resulted in modifications in the traditional paradigms for managing this aspect., Recent Findings: Regardless of the pretreatment neck staging, patients who have a complete response to chemoradiation are unlikely to have residual viable tumor in this region, thus putting in question the need for planned neck dissection. F-Fluorodeoxyglucose positron emission tomography/computed tomography has become a standard tool to assess disease response to chemoradiotherapy, including the associated nodal disease. However, there remains an ongoing debate about its timing. The extent of neck dissection is trending toward an approach for selective procedures in order to minimize the long-term sequelae of extensive neck fibrosis., Summary: Post-chemoradiotherapy neck dissection is an effective procedure for selected patients with advanced head and neck cancer but is becoming a less needed intervention.

Background: Multiple modalities have been used to treat the stiff TKA, including manipulation under anesthesia (MUA), arthroscopy, and open arthrolysis., Questions/purposes: We reviewed the literature to address three questions: (1) How many degrees of ROM will a stiff TKA gain after MUA, arthroscopy, and open arthrolysis? (2) Does the timing of each procedure influence this gain in ROM? (3) What is the number of clinically important complications for each procedure?, Methods: We performed a PubMed search of English language articles from 1966 to 2008 and identified 20 articles, mostly Level IV studies., Results: For patients who have arthrofibrosis after TKA, the gains in ROM after MUA and arthroscopy (with or without MUA) are similar. Open arthrolysis seems to have inferior gains in ROM. MUA is more successful in increasing ROM when performed early but still may be effective when performed late. Arthroscopy combined with MUA still is useful 1 year after the index TKA. The numbers of clinically important complications after MUA and arthroscopy (with or without MUA) are similar., Conclusions: Stiffness after TKA is a common problem that can be improved with MUA and/or arthroscopic lysis of adhesions with few complications. The low quality of available literature makes it difficult to develop treatment protocols., Level of Evidence: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Object: Epineural fibrosis may complicate peripheral nerve surgeries and currently is considered as one of the main factors responsible for failed surgeries. The authors investigated the postoperative antiscarring effects of topically applied doxorubicin (DXR) on rat sciatic nerves., Methods: The sciatic nerves were dissected from the surrounding tissue and exposed bilaterally in 20 Wistar albino adult male rats. Abrasion trauma was produced on the exposed surface of the biceps femoris muscle in the vicinity of the sciatic nerves and their main branches in all animals. In the DXR Group, cottonoid pads soaked with DXR (0.5 mg/ml) were placed around the nerves for 5 minutes, whereas cotton pads soaked with saline (0.9% NaCl) were applied to nerves of animals in the Control Group for the same duration. Twelve weeks after the procedure, all of the rats were killed and the sciatic nerves were examined. Epineural adhesions were evaluated histopathologically and ultrastructurally. Additionally, quantitative histological parameters, the scar tissue formation index and the scar density, were calculated in histological evaluation., Results: Gross postsurgical evaluation as well as histopathological and electron microscopic examination of involved nerve segments showed significantly less epineurial adhesions in the DXR Group than in the Control Group. Quantitative analysis of the epineurium revealed a statistically significant reduction in the density and amount of epineural scarring in specimens from the DXR Group than in those from the Control Group., Conclusions: The results of gross postsurgical anatomical evaluation and histopathological and ultrastructural studies suggested that topical application of DXR effectively reduced epineural scar formation on rat sciatic nerves. These promising findings merit further experimental and clinical studies to determine the efficacy and safe applicability of DXR in human subjects.

This study investigates a cohort of patients who required a manipulation after total knee arthroplasty (TKA) to determine whether there was an association between pre-TKA and post-manipulation range of motion (ROM). Thirty-seven of 800 TKAs were manipulated (4.6% incidence); complete data were available for 36 knees. The pre-TKA stiff group (<110 degrees total arc of motion; n=16), on average, had 27 degrees less arc of motion before TKA than the non-stiff group (n=20; p<0.001). Mean arc of motion in the stiff group was 68 degrees before manipulation and 109 degrees after manipulation (p<0.001). Mean arc of motion in the non-stiff group was 80 degrees before manipulation and 118 degrees after manipulation (p<0.001). Patients with pre-TKA stiffness improved from a total arc of motion of 94 to 109 (p<0.001) while patients without pre-TKA stiffness changed from 121 to 118 (p=0.169). In both groups, the success of TKA can still be high despite early motion loss and subsequent manipulation.

Background: Epidural fibrosis (EF) is defined as nonphysiologic scar formation, usually at the site of neurosurgical access into the spinal canal, in intimate vicinity to and around the origin of the radicular sheath. From the very onset, EF behaves as a reparative inflammation causing, as a rule, clinical problems of characteristic nature and dynamism (pain). Treatment for EF, the role and mode of application of corticosteroids for EF management are, to this day, a moot point in algesiologic literature. The authors conducted a prospective study designed to obtain new data for assessing the anti-inflammatory effects of corticosteroids with special regard to the part played by steroids in the development of EF. The study also aimed at rating EF in terms of its effects on the intensity and character of the patient's symptoms after surgery for herniated intervertebral disc in the lumbar region., Method: A double-blind prospective study was conducted to investigate a cohort of 200 patients requiring surgical treatment for intervertebral disc hernia (hernia disci intervertebralis). The patients were randomly and blindly divided into 2 groups, one on peroperatively applied local doses of a mix containing corticosteroids, the other without such medication. All the requirements of a double-blind study, including statistical assessment of the results, were observed throughout the diagnostic and therapeutical processes. The results were processed relative to the: clinical finding, subjective intensity of symptoms rated on a visual analog scale, radiographic finding (magnetic resonance imaging: plain and after contrast medium application)., Results: A statistical comparison of the clinical picture in the 2 surgically treated groups failed to reach statistical significance. Nevertheless, a trend toward better clinical picture in the steroid mix group was observed. Paradoxically, when statistically compared, the rate of EF build-up was found greater in the steroid-treated group. A 5% statistical significance was established in the correlation between the presence of EF and the patients' subjective rating (difference between input and output visual analog scale).

Postlaminectomy epidural adhesion is implicated as a main cause of "failed back surgery syndrome" and associated with increased risk of complications during revision surgery. Various materials acting as mechanical barriers to reduce fibroblasts infiltration into epidural space have met with limited success. In present research, amniotic membrane (AM) was studied to investigate its effects on reducing epidural scar adhesion after laminectomy in a canine model. Laminectomy sites were created at L-1, L-3, L-5, and L-7 levels in 24 adult mongrel dogs. Freeze dried AM (FAM), cross-linked AM (CAM), and autologous free fat (AFF) were implanted, respectively, at a randomly assigned site in each dog with the remaining untreated site serving as internal control. The animals were sacrificed at 1, 6, and 12 weeks postoperatively. Then, gross pathologic observation including scar amount and adhesion tenacity, qualitative histology evaluation, and quantitative histology analysis were compared. Gross observation demonstrated that scar amount and adhesion tenacity of CAM group were significantly lower in comparison with those of FAM and non-treatment groups. A white, slightly vascularized CAM layer covered the dura mater without tenacious scar adhesion. The histology analysis also indicated reduced fibroblasts infiltration and consequent epidural fibrosis, which were similar to the results of AFF group. In conclusion, the CAM is effective in reducing epidural fibrosis and scar adhesion after laminectomy in canine model. It is a promising biomaterial for future clinical applications.

Mondor's disease is an uncommon complication of breast and axillary surgery. Although self-limiting, the subcutaneous cords may be both painful and functionally limiting for the patient. Numerous pharmacologic approaches have been tried, but without widespread success, and we wished to evaluate the non-invasive technique of manual axial distraction in such patients. Thirty consecutive patients with axillary Mondor's disease following surgery were treated solely with this technique by the senior author (RJS) over a 24-month period. Mean age was 45 years (range 32-72) with 27 having undergone formal axillary dissection and three sentinel node biopsy. 25 (83.3%) were successfully treated with a single procedure, three (10%) with two and two (6.7%) with three procedures. we present the initial results of the novel technique of manual axial distraction that has been found to be efficacious and without adverse effect. It provides a rapid and definitive cure in postoperative Mondor's disease.

The EORTC 22881-10882 trial in 5178 conservatively treated early breast cancer patients showed that a 16 Gy boost dose significantly improved local control, but increased the risk of breast fibrosis. To investigate predictors for the long-term risk of fibrosis, Cox regression models of the time to moderate or severe fibrosis were developed on a random set of 1797 patients with and 1827 patients without a boost, and validated in the remaining set. The median follow-up was 10.7 years. The risk of fibrosis significantly increased (P<0.01) with increasing maximum whole breast irradiation (WBI) dose and with concomitant chemotherapy, but was independent of age. In the boost arm, the risk further increased (P<0.01) if patients had post-operative breast oedema or haematoma, but it decreased (P<0.01) if WBI was given with >6 MV photons. The c-index was around 0.62. Nomograms with these factors are proposed to forecast the long-term risk of moderate or severe fibrosis.