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Background: CD300a is an inhibitory receptor (IR) expressed on several leukocytes, including mast cells (MCs) and macrophages (MΦ), important cells in allergic inflammation (AI). We have previously characterized CD300a role on MCs and in vivo in mouse models of allergy, in which the absence of CD300a resulted in increased inflammatory features and delayed resolution. However, the exact mechanism of this delayed resolution is unclear. Our hypothesis is that MΦ, important players in resolution, might be impaired when CD300a is absent. Objectives: The aim of the study was to investigate CD300a-dependent functionality of mouse MΦ. Method: MΦ were purified from the peritoneum of wild-type (WT) and CD300a−/− mice naïve and 48 h and 96 h after challenge with ovalbumin/alum. Phenotype switching was analyzed via specific M1-M2 inducers and markers. MΦ phagocytotic ability was assessed via Staphylococcus aureus pHrodo-conjugated bioparticles. The influence of MCs on MΦ was investigated by incubating WT MΦ with supernatants from non-activated and IgE-activated bone marrow-derived MCs (BMMCs) and analyzing functional responses. Results: Naïve CD300a−/− MΦ presented with increased sensitivity to activation when treated with LPS. Absence of CD300a results in increased Arg1 expression and increased IL-6 release when MΦ are purified from allergic peritonitis-induced mice. Similar results were obtained when CD300a−/− MΦ were purified 96 h after challenge. On the other hand, CD300a absence did not affect phagocytosis. WT MΦ incubated with supernatants of non-activated and IgE-activated BMMCs presented with increased iNOS expression and decreased Arg1 levels. Conclusions: The IR CD300a controls the activation state of MΦ, and its absence could augment the inflammatory state seen in CD300a−/− mice. Moreover, MCs can also influence MΦ phenotype switching. This may partially explain the delayed AI resolution seen in these mice. [ABSTRACT FROM AUTHOR]

Background: Osteochondral allograft transplantation (OCAT) is an accepted knee joint–preserving treatment strategy for focal osteochondral lesions that is often conducted in combination with meniscal allograft transplantation (MAT). Despite its frequent and simultaneous utilization, there remains a lack in the literature reporting on outcomes and failure rates after concomitant procedures. Purpose: To determine (1) the midterm clinical success rate after OCAT+MAT in comparison with a matched-pair cohort undergoing isolated OCAT, (2) whether patient-specific and procedural variables influence the risk of failure, and (3) patient-reported outcome measures over time. Study Design: Cohort study; Level of evidence, 3. Methods: A single-center matched-pair cohort study was conducted investigating outcomes in patients who underwent OCAT of the medial or lateral femoral condyle with and without MAT between 2004 and 2020. Patients were matched 1:1 by age (±5 years), sex (male or female), body mass index (±5), and grouped Kellgren and Lawrence grade (grades 0-1 or 2-4). The minimum follow-up time was 2 years. Radiographic variables (International Cartilage Regeneration & Joint Preservation Society [ICRS] grade and Kellgren and Lawrence grade) were assessed preoperatively and at follow-up. Subjective patient-reported outcome measures (Lysholm score, Knee injury and Osteoarthritis Outcome Score [KOOS] including subscores, International Knee Documentation Committee [IKDC] score, and visual analog scale score) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery for graft failure or conversion to total knee arthroplasty. Patient-reported, clinical, and radiographic outcomes were compared between groups. Results: In total, 66 patients (33 treated with isolated OCAT, 33 treated with OCAT+MAT; 57.6% male) with a mean age of 26.3 years (range, 18-62 years) were followed for a mean of 5.6 years (minimum, 2 years; range, 24-218 months). The 2 cohorts showed no difference in Kellgren and Lawrence grade postoperatively (P =.59). There was a significantly higher ICRS grade detected at follow-up in the OCAT+MAT group (2.81 ± 1.10) compared with the OCAT group (2.04 ± 0.96) (P <.05). There were no statistically significant differences between the groups regarding reoperation rate (OCAT: n = 6; OCAT+MAT: n = 13; P =.116), time to reoperation (OCAT: 46.67 ± 47.27 months vs OCAT+MAT: 28.08 ± 30.16 months; P =.061), and failure rate (OCAT: n = 4 [12.1%] vs OCAT+MAT: n = 5 [15.2%]; P =.66). In the OCAT+MAT group, an increase of tibial slope by 1° conferred a 1.65-fold increase in the hazard for failure over decreased slope (hazard ratio, 1.65; 95% CI, 1.10-2.50; P <.05). The overall survival rate was 86% at a mean follow-up of 5.6 years. Patient-reported outcome scores were significantly improved at the final follow-up compared with preoperative status. No significant differences were seen between groups with respect to subjective IKDC, Lysholm, Tegner, and KOOS results, except for the KOOS Symptoms subscale score, which was significantly higher in the OCAT+MAT group than in the OCAT group (mean difference, 14.6; P <.05) and did exceed the minimal clinically important difference threshold of 10.7. Conclusion: Midterm results after isolated OCAT and OCAT+MAT show high rates of healing and sustainable subjective improvement of knee function and quality of life. However, it should be noted that the difference in reoperation rate and time to reoperation between the groups is arguably clinically important and that lack of statistical significance may be because of low power. These results imply that isolated OCAT is an efficient joint-preserving treatment that can be combined with MAT in well-selected patients with meniscal insufficiency without negative influence on global clinical outcomes. [ABSTRACT FROM AUTHOR]

The article presents the author's views on the aspects of posterior cruciate ligament (PCL) reconstruction and how to create the tibial socket for PCL reconstruction. Topics discussed includes combined ACL/PCL reconstructions, need of proper socket placements on both the femoral and tibial sides and anterolateral and posteromedial PCL remnants.

Countless times each day, the acute inflammatory response protects us from invading microbes, injuries, and insults from within, as in surgery-induced tissue injury. These challenges go unnoticed because they are self-limited and naturally resolve without progressing to chronic inflammation. Peripheral blood markers of inflammation are present in many common diseases, including inflammatory bowel disease, cardiovascular disease, neurodegenerative disease, and cancer. While acute inflammation is protective, excessive swarming of neutrophils amplifies collateral tissue damage and inflammation. Hence, understanding the mechanisms that control the resolution of acute inflammation provides insight into preventing and treating inflammatory diseases in multiple organs. This Review focuses on the resolution phase of inflammation with identification of specialized pro-resolving mediators (SPMs) that involve three separate biosynthetic and potent mediator families, which are defined using the first quantitative resolution indices to score this vital process. These are the resolvins, protectins, and maresins: bioactive metabolomes that each stimulate self-limited innate responses, enhance innate microbial killing and clearance, and are organ-protective. We briefly address biosynthesis of SPMs and their activation of endogenous resolution programs as terrain for new therapeutic approaches that are not, by definition, immunosuppressive, but rather new immunoresolvent therapies. [ABSTRACT FROM AUTHOR]

Essential fatty acids can serve as important regulators of inflammation. A new window into mechanisms for the resolution of inflammation was opened with the identification and structural elucidation of mediators derived from these fatty acids with pro-resolving capacity. Inflammation is necessary to ensure the continued health of the organism after an insult or injury; however, unrestrained inflammation can lead to injury “from within” and chronic changes that may prove both morbid and fatal. The resolution phase of inflammation, once thought to be a passive event, is now known to be a highly regulated, active, and complex program that terminates the inflammatory response once the threat has been contained. Specialized pro-resolving mediators (SPMs) are biosynthesized from omega-3 essential fatty acids to resolvins, protectins, and maresins and from omega-6 fatty acids to lipoxins. Through cell-specific actions mediated through select receptors, these SPMs are potent regulators of neutrophil infiltration, cytokine and chemokine production, and clearance of apoptotic neutrophils by macrophages, promoting a return to tissue homeostasis. This process appears to be defective in several common human lung diseases, such as asthma and COPD, which are characterized by chronic unrestrained inflammation and significant associated morbidity. Here, we highlight translational research in animal models of disease and with human subjects that sheds light on this rapidly evolving area of science and review the molecular and cellular components of the resolution of lung inflammation. [ABSTRACT FROM AUTHOR]

The article offers information regarding Role of Arthroscopic Partial Meniscectomy in the Treatment of Meniscal Tears. It mentions that treating reating symptomatic degenerative meniscal tears used to be relatively straightforward. Some surgeons would recommend physical therapy and a cortisone injection followed by surgery if nonoperative treatment did not relieve pain, while others recommended surgery as soon as they identified a tear.

Purpose: To compare the accuracy and reliability of the anatomic and radiographic techniques for identifying the isometric point of the knee. Methods: Only four specimens were used; however, eight experienced multiligament knee injury surgeons were recruited to address this limitation. Surgeons estimated the isometric point (EIP) on the medial and lateral sides using an anatomic and radiographic method. The x and y coordinates of the EIP were compared to the true isometric point (TIP). T-tests and interclass correlation coefficients (ICC) were performed to determine the accuracy and reliability between the methods. Results: There was no difference in placement of the EIP on the medial side of the knee in the anterior/posterior ( x; p = n.s.) and superior/inferior direction ( y; p = n.s). The EIP was anterior ( p = 0.001) to the TIP with the radiographic method on the lateral side and approached significance ( p = 0.05) in the superior/inferior direction. The ICC (95 % CI) for identifying the EIP on the medial side in the anterior/posterior direction using the anatomic method was 0.64 (0.28-0.96) and 0.11 (−0.06 to 0.77) in the superior/inferior direction. Using the radiographic method, the ICC in the anterior/posterior and superior/inferior direction was 0.49 (0.14-0.94) and 0.15 (−0.47 to 0.81), respectively. On the lateral side, the ICC for the anatomic method was 0.84 (0.56-0.99) in the anterior/posterior direction and 0.36 (0.05-0.90) in the superior/inferior direction. Using the radiographic method, the ICC in the anterior/posterior and superior/inferior direction was 0.61 (0.26-0.96) and 0.89 (0.67-0.99), respectively. Conclusions: There was no difference in accuracy on the medial side of the knee. On the lateral side, the anatomic method was more accurate in the anterior/posterior direction. Reliability was greater in the anterior/posterior direction on both sides of the knee. Surgeons were most likely to place the isometric point anterior and superior to the TIP on both the medial and lateral sides of the knee with either method which has the potential to cause graft lengthening. This should be taken into consideration during reconstruction/repair of the MCL/PMC and LCL/PLC. [ABSTRACT FROM AUTHOR]

Acute inflammation in the lung is essential to health. So too is its resolution. In response to invading microbes, noxious stimuli, or tissue injury, an acute inflammatory response is mounted to protect the host. To limit inflammation and prevent collateral injury of healthy, uninvolved tissue, the lung orchestrates the formation of specialized proresolving mediators, specifically lipoxins, resolvins, protectins, and maresins. These immunoresolvents are agonists for resolution that interact with specific receptors on leukocytes and structural cells to blunt further inflammation and promote catabasis. This process appears to be defective in several common lung diseases that are characterized by excess or chronic inflammation. Here, we review the molecular and cellular effectors of resolution of acute inflammation in the lung. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To evaluate relative fracture stability yielded by screws placed above a lateral plate, as well as locking and non-locking screws placed through a plate in a split depression tibia plateau fracture model. Methods: Cadaver tibia specimens (mean age 74.1 years) were randomised across 3 groups: Groups 1: raft-construct outside the plate, 2: non-locking raft screws through the plate, and 3: locking raft screws through the plate. Displacement of the depressed fragment was recorded with force values from 400N to 1600N in increasing 400N increments. The force required to elicit lateral plateau fragment displacement of 5mm, 10mm, and 15mm was also recorded. Results: None of the mechanical testing results demonstrated statistical significance with p-values of <0.05. Cyclic testing of Groups 1, 2, and 3 at 400N revealed displacements of 0.54mm, 0.64mm, and 0.48mm, respectively. At 800N, displacements were 1.36mm, 1.4mm, and 1.4mm, respectively. At 1200N, displacements were 2.4mm, 1.9mm, and 2.1mm, respectively. At 1600N, displacements were 2.8mm, 2.5mm, and 2mm, respectively. Resistance to displacement data demonstrated the mean force required to displace the fracture 5mm in Groups 1, 2, and 3 were 250N, 330N, and 318N, respectively. For 10mm of displacement, forces required were 394N, 515N, and 556N, respectively. For 15mm of displacement, forces required were 681N, 853N, and 963N, respectively. Compared to combined groups using screws through the plate, Group 1 demonstrated lower displacement ≤800N, but demonstrated greater displacement >800N. Group 2 demonstrated greatest resistance to plateau displacement of 5mm compared to Group 1 or 3, while Group 3 was most resistant to greater displacement. The combined group using screws through the plate (Groups 2+3) was consistently more resistant than Group 1 at all levels of displacement. Conclusions: Designs utilising screws through the plate trended towards statistically significant improved stability against plateau displacement relative to utilising screws outside the plate. Our study also suggests that there is no significant benefit of locking screws over non-locking screws in this unicondylar tibia plateau fracture model. [Copyright &y& Elsevier]

Purpose: The primary purpose of this study was to investigate the intra-tester and inter-tester reliability of the dial test using a handheld digital inclinometer. Additionally, we examined the responsiveness of the test, and side-to-side differences for meaningful comparison. Materials/methods: Twenty-four healthy subjects (22.5 ± 2.8 years) participated in the study. The dial test was performed on both knees at 30° and 90° of knee flexion with the subject supine. While maintaining a neutral position of the ankle, an inclinometer was positioned parallel to the medial border of the foot to quantify external rotation of the tibia. Two examiners performed the dial test in a blinded manner. The minimal detectable change across repeated measures and side-to-side difference was calculated. Results: Intra-tester reliability for examiner 1 (E1) was 0.83 at 30° knee flexion and 0.89 at 90° knee flexion. Reliability values for examiner 2 (E2) were 0.86 at 30° and 0.87 at 90° knee flexion. Inter-tester reliability was 0.74 at 30° and 0.83 at 90°. The minimal detectable change (MDC) for E1 at 30° was ±9.4° and ±7.4° at 90°. For E2, the MDC value was ±9.1° at 30° and ±8.3° at 90°. Ninety-five percent limits of agreement for side-to-side difference was 16.1° and 11.3° ° for E1 at 30° and 90° and for E2 13.9° at 30° and 14.1° at 90°. Conclusions: This instrumented dial test using a handheld digital inclinometer to measure external rotation can be performed with acceptable reliability in the clinical setting. A difference of 10° between two measurements on the same knee suggests that a meaningful change has occurred. For right to left comparison, differences greater than 15° suggest clinical significance. Level of evidence: III. [ABSTRACT FROM AUTHOR]

The article focuses on the surgical treatment for acute and chronic posterior cruciate ligament (PCL) and anterior cruciate ligament (ACL) and lateral side knee injuries that usually result from knee dislocation. It explores the diagnosis, neurovascular assessment, and surgical timing, as well as the role of proximal tibial osteotomy in treating multi-ligament knee injury. It suggests the measurement of ankle brachial index (ABI) on multi-ligament knee injury and vascular imaging if needed.

Purpose: The purpose of this study is to determine the effect of bioabsorbable interference screw (BIS) tibial fixation with the Delta screw (antegrade) and RetroScrew (retrograde) on initial (time zero) intra-articular graft tension in soft tissue anterior cruciate ligament (ACL) reconstruction in a cadaveric model. Methods: Ten matched pairs of cadaveric tibias received one of two tibial fixation constructs using quadrupled hamstring grafts, Delta screw (antegrade) or the RetroScrew (retrograde). Each specimen was mounted to the materials testing device with the displacement force vector in line with the tibial tunnel. The construct was pre-tensioned (10-30 N, 0.1 Hz, 10 cycles), a baseline tension of 25 N was introduced, and the change in intra-articular graft tension before and after screw insertion was recorded. Results: Segmental (proximal, middle, distal) BMD was utilized to assess BMD using quantitative computed tomography (qCT). The Delta screw had a higher maximum insertion torque ( P = 0.03) and exhibited a larger increase in intra-articular graft tension as compared to the RetroScrew (38.3 ± 17.9 N, 7.6 N ± 14.4, P = 0.004), respectively. There were no significant correlations between intra-articular graft tension increase to maximum insertion torque ( P = NS) or corresponding segmental BMD ( P = NS). Conclusions: Delta screw tibial fixation (antegrade) in soft tissue ACL reconstruction significantly increases the initial intra-articular graft tension as compared to RetroScrew screw fixation (retrograde) in this cadaveric model. Delta screw (antegrade) tibial fixation may increase initial quadrupled hamstring graft intra-articular tension with currently accepted insertion techniques. [ABSTRACT FROM AUTHOR]

Abstract: Inappropriate or excessive pulmonary inflammation can contribute to chronic lung diseases. In health, the resolution of inflammation is an active process that terminates inflammatory responses. The recent identification of endogenous lipid-derived mediators of resolution has provided a window to explore the pathobiology of inflammatory disease and structural templates for the design of novel pro-resolving therapeutics. Resolvins (resolution-phase interaction products) are a family of pro-resolving mediators that are enzymatically generated from essential omega-3 polyunsaturated fatty acids. Two molecular series of resolvins have been characterised, namely E- and D-series resolvins which possess distinct structural, biochemical and pharmacological properties. Acting as agonists at specific receptors (CMKLR1, BLT1, ALX/FPR2 and GPR32), resolvins can signal for potent counter-regulatory effects on leukocyte functions, including preventing uncontrolled neutrophil swarming, decreasing the generation of cytokines, chemokines and reactive oxygen species and promoting clearance of apoptotic neutrophils from inflamed tissues. Hence, resolvins provide mechanisms for cytoprotection of host tissues to the potentially detrimental effects of unresolved inflammation. This review highlights recent experimental findings in resolvin research, and the impact of these stereospecific molecules on the resolution of pulmonary inflammation and tissue catabasis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was (1) to describe a staged protocol for management of the dislocated knee and (2) to describe clinical and functional outcomes for patients who received initial spanning external fixation as part of this protocol. Method: Nine knees in 9 patients, consisting of 6 males and 3 females, mean age 30.4 (range 19-44) years with diagnosis or presumption of knee dislocation were treated with a protocol of stabilization with external fixator. Mean follow-up was 24 (range 13-42) months. Indications for spanning external fixation included significant vascular injury, gross instability on examination with failure to maintain joint reduction, open knee dislocation, inability to tolerate mobilization in a brace. The standard protocol involved vascular examination including ankle-brachial index, ligamentous examination (under anesthesia when applicable), stabilization with temporary joint spanning external fixator, thromboprophylaxis, reconstructive knee surgery, and standard rehabilitation. Results: Mean range of motion (ROM) was 97.4° (range 80°-150°, SD 20.75, median 127.5). Median IKDC score was 80 (range 30-95), and mean Lysholm score was 76.7 (range 46-95). Heterotopic ossification (HO) was noted in 4 knees (44%). Conclusion: The treatment algorithm utilized in this series for management of the dislocated knee demonstrated satisfactory clinical and functional outcomes. This staged protocol provides a management option for those patients who may be best served with initial spanning joint external fixation. Larger prospective studies are needed to fully understand the merit of staged protocols in this setting. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the injuries occurred in the fibular collateral ligament (FCL) and posterolateral corner (PCL) of the knee. The study identifies that the FCL/PCL injuries can be diagnosed through physical examination and other types of diagnostic imaging such as the magnetic resonance imaging (MRI). Moreover, the study discusses that the FCL/PCL injuries applies the combination of hyperextension and varus forces as its most common mechanism.

Purpose: Numerous surgical techniques have been described for the treatment of peroneal nerve palsy after knee dislocation with less than optimal outcomes. The purpose of this article is to present a review of the literature including modern surgical treatment options for peroneal nerve palsy after knee dislocation. Method: Review of the current body of literature relevant to the topic was undertaken and summarized accordingly. Mechanism of injury, pathology and prognosis as well as current and novel treatment options are presented. Results: Neurolysis and nerve grafting results are dependant on nerve graft length, with documented recovery rates of only 44% for nerve grafts longer than 6 cm. Posterior tibial tendon transfer procedures have had reasonable success in allowing patients to return to ambulation without assistive devices; however, dorsiflexion strength on the affected side has been reported at only 30% that of the normal contralateral side, and return to activities more strenuous than walking has not been reported. Future concepts including partial nerve transfer of a motor branch of the tibial nerve to the peroneal nerve have been described, but no outcome data is currently available. Conclusion: Peroneal nerve palsy after knee dislocation leads to significant functional impairment. Prior treatment strategies utilized for restoration of dorsiflexion and peroneal nerve function have yielded overall poor results. Newer surgical techniques are being developed and clinical trials are under way to evaluate their effectiveness. [ABSTRACT FROM AUTHOR]

Background: Treatment of the multiligament-injured knee remains controversial. Purpose: To compare clinical and functional outcomes of a consecutive series of multiligament-injured knees that underwent repair of the fibular collateral ligament (FCL) and posterolateral corner (PLC), followed by delayed cruciate ligament reconstructions, with those that had single-stage multiligament reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: Patients with multiligament knee injury treated by a single surgeon were identified in our prospective database. Between February 2004 and May 2005, patients underwent repair of medial- and lateral-sided injuries, followed by delayed cruciate ligament reconstructions. Between May 2005 and February 2007, patients underwent single-stage multiligament knee reconstruction. All patients followed a standard rehabilitation protocol. Inclusion criteria were minimum 2-year follow-up and multiligament knee injury including the FCL/PLC. International Knee Documentation Committee subjective and Lysholm scores and objective clinical data were documented. Results: We identified 45 knees (42 patients); 17 knees (14 patients) were excluded, leaving 28 knees (28 patients) in the study. The repair/staged group (10 knees in 10 patients) had a mean follow-up of 34 months (range, 24-49 months). The reconstruction group (18 knees in 18 patients) had a mean follow-up of 28 months (range, 24-41 months). Four of the 10 FCL/PLC repairs (40%) and 1 of the 18 FCL/PLC reconstructions (6%) failed (P = .04). After revision reconstructions, there were no statistically significant differences between mean International Knee Documentation Committee subjective scores (79 vs. 77, P = .92) and mean Lysholm scores (85 vs 88, P = .92). Regression analysis showed no effect on failure based on age, sex, injury mechanism, time to surgery, interval between stages, total number of ligaments injured, or location of tear. Conclusion: Our series demonstrated a statistically significant higher rate of failure for repair compared with reconstruction of the FCL/PLC. Reconstruction of the FCL/PLC structures is a more reliable option than repair alone in the setting of a multiligament knee injury [ABSTRACT FROM AUTHOR]

Background: An imbalance in the generation of pro-inflammatory leukotrienes, and counter-regulatory lipoxins is present in severe asthma. We measured leukotriene LTB4 (LTB4), and lipoxin A4 (LXA4) production by alveolar macrophages (AMs) and studied the impact of corticosteroids. Methods: AMs obtained by fiberoptic bronchoscopy from 14 non-asthmatics, 12 non-severe and 11 severe asthmatics were stimulated with lipopolysaccharide (LPS,10 μg/ml) with or without dexamethasone (10-6M). LTLTB4 and LXA4 were measured by enzyme immunoassay. Results: LXA4 biosynthesis was decreased from severe asthma AMs compared to non-severe (p < 0.05) and normal subjects (p < 0.001). LXA4 induced by LPS was highest in normal subjects and lowest in severe asthmatics (p < 0.01). Basal levels of LTLTB4 were decreased in severe asthmatics compared to normal subjects (p < 0.05), but not to non-severe asthma. LPS-induced LTLTB4 was increased in severe asthma compared to non-severe asthma (p < 0.05). Dexamethasone inhibited LPS-induced LTLTB4 and LXA4, with lesser suppression of LTLTB4 in severe asthma patients (p < 0.05). There was a significant correlation between LPS-induced LXA4 and FEV1 (% predicted) (rs = 0.60; p < 0.01). Conclusions: Decreased LXA4 and increased LTLTB4 generation plus impaired corticosteroid sensitivity of LPS-induced LTLTB4 but not of LXA4 support a role for AMs in establishing a pro-inflammatory balance in severe asthma. [ABSTRACT FROM AUTHOR]

Patient activity level may be an important prognostic variable relating to outcome in patients with shoulder disorders. The purpose of this cross-sectional study was to test the hypothesis that a shoulder activity scale will detect differences in shoulder activity based on the patient diagnosis and age. A total of 157 patients of four academic orthopedic surgeons with a diagnosis of rotator cuff disease (86), glenohumeral instability (31) or osteoarthritis (40) were asked to fill out a previously validated shoulder activity scale and the ASES shoulder questionnaire. The patient’s diagnosis, gender and age were recorded. The activity level was significantly higher in patients with instability than in patients with rotator cuff disease or osteoarthritis. Patients with rotator cuff disease were significantly more active than patients with osteoarthritis. Linear regression of activity level on patient age and diagnosis demonstrated a statistically significant relationship between activity level and both independent variables. Diagnosis influenced activity level independent of age. This is the first study to document diagnosis-based differences in the shoulder activity level of patients with different shoulder disorders. Shoulder activity level should be evaluated as a prognostic variable in studies of patients with shoulder disorders that may predict outcome and guide treatment in these patients. [ABSTRACT FROM AUTHOR]

Resolution of inflammation has historically been viewed as a passive process, occurring as a result of the withdrawal of pro-inflammatory signals, including lipid mediators such as leukotrienes and prostaglandins. Thus, most anti-inflammatory drugs have traditionally targeted primarily mediator pathways that are engaged at the onset of inflammation. Only recently has it been established that inflammation resolution is an active process with a distinct set of chemical mediators. Several clinical and epidemiological studies have identified beneficial effects of polyunsaturated fatty acids (PUFAs) for a variety of inflammatory diseases, yet without mechanistic explanations for these beneficial effects. Resolvins and protectins are recently identified molecules that are generated from omega-3 PUFA precursors and can orchestrate the timely resolution of inflammation in model systems. Dysregulation of pro-resolving mediators is associated with diseases of prolonged inflammation, so designing pharmacological mimetics of naturally occurring pro-resolving mediators offers exciting new targets for drug design. This review describes the discovery and synthesis of these novel lipid mediators, their receptors and mechanisms of action, and summarizes the studies to date that have uncovered roles for resolvins and protectins in disease states. [ABSTRACT FROM AUTHOR]

Tetrahydrobiopterin (BH4) is a key redox-active cofactor in endothelial isoform of NO synthase (eNOS) catalysis and is an important determinant of NO-dependent signaling pathways. BH4 oxidation is observed in vascular cells in the setting of the oxidative stress associated with diabetes. However, the relative roles of de novo BH4 synthesis and BH4 redox recycling in the regulation of eNOS bioactivity remain incompletely defined. We used small interference RNA (siRNA)-mediated "knock-down" GTP cyclohydrolase-1 (GTPCH1), the rate-limiting enzyme in BH4 biosynthesis, and dihydrofolate reductase (DHFR), an enzyme-recycling oxidized BH4 (7,8-dihydrobiopterin (BH2)), and studied the effects on eNOS regulation and biopterin metabolism in cultured aortic endothelial cells. Knockdown of either DHFR or GTPCH1 attenuated vascular endothelial growth factor (VEGF)-induced eNOS activity and NO production; these effects were recovered by supplementation with BH4. In contrast, supplementation with BH2 abolished VEGF-induced NO production. DHFR but not GTPCH1 knockdown increased reactive oxygen species (ROS) production. The increase in ROS production seen with siRNA-mediated DHFR knockdown was abolished either by simultaneous siRNA-mediated knockdown of eNOS or by supplementing with BH4. In contrast, addition of BH2 increased ROS production; this effect of BH2 was blocked by BH4 supplementation. DHFR but not GTPCH1 knockdown inhibited VEGF-induced dephosphorylation of eNOS at the inhibitory site serine 116; these effects were recovered by supplementation with BH4. These studies demonstrate a striking contrast in the pattern of eNOS regulation seen by the selective modulation of BH4 salvage/reduction versus de novo BH4 synthetic pathways. Our findings suggest that the depletion of BH4 is not sufficient to perturb NO signaling, but rather that concentration of intracellular BH2, as well as the relative concentrations of BH4 and BH2, together play a determining role in the redox regulation of eNOS-modulated endothelial responses. [ABSTRACT FROM AUTHOR]

Asthma pathobiology is remarkable for chronic airway inflammation that fails to spontaneously resolve. No curative therapy is currently available. A growing body of evidence indicates that, in health, inflammation resolution is an active process orchestrated by specific chemical mediators that are elaborated to restore tissue homeostasis. Activated cell membranes release polyunsaturated fatty acids from phospholipids for enzymatic conversion to biologically active mediators with profound regulatory effects on innate and adaptive immunity. Some of these mediators carry anti-inflammatory and pro-resolving actions that are transduced in a cell-type specific manner via specific recognition sites that initiate regulatory intracellular signals, such as presqualene diphosphate remodeling, to limit pro-phlogistic cell activation. Some of these counter-regulatory lipid mediators have been identified in the airway during asthma and defects in their production are associated with disease severity. In this review, we describe the biosynthesis and bioactions of pro-resolving chemical mediators and provide examples of select mediators and their structural analogs with particular relevance to asthma. [ABSTRACT FROM AUTHOR]

Cellular recruitment during inflammatory/ immune responses is tightly regulated. The ability to dampen inflammation is imperative for prevention of chronic immune responses, as in asthma. Here we investigated the ability of lipoxin A4 (LXA4) stable analogs to regulate airway responses in two allergen-driven models of inflammation. A 15-epi-LXA4 analog (ATLa) and a 3-oxa-15-epi-LXA4 analog (ZK-994) prevented excessive eosinophil and T lymphocyte accumulation and activation after mice were sensitized and aerosol-challenged with ovalbumin. At <0.5 mg/kg, these LXA4 analogs reduced leukocyte trafficking into the lung by >50% and to a greater extent than equivalent doses of the CysLT1 receptor antagonist montelukast. Distinct from montelukast, ATLa treatment led to marked reductions in cysteinyl leukotrienes, interleukin-4 (IL-4), and IL-10, and both ATLa and ZK-994 inhibited levels of IL-13. In cockroach allergen-induced airway responses, both intraperitoneal and oral administration of ZK-994 significantly reduced parameters of airway inflammation and hyper-responsiveness in a dose-dependent manner. ZK-994 also significantly changed the balance of Th1/Th2-specific cytokine levels. Thus, the ATLa/LXA4 analog actions are distinct from CysLT1 antagonism and potently block both allergic airway inflammation and hyper-reactivity. Moreover, these results demonstrate these analogs' therapeutic potential as new agonists for the resolution of inflammation. [ABSTRACT FROM AUTHOR]

Leukocyte production of reactive oxygen species (ROS) is an essential component of the antimicrobial armament mounted during host defense, but when released to the extracellular milieu ROS can also injure host tissues and provoke inflammation. Polyisoprenyl phosphates (PIPPs) are constituents of human leukocyte membranes that regulate pivotal intracellular enzymes, such as phospholipase D (PLD). We prepared new PIPP mimetics and studied their impact in vivo on leukocyte activation, including ROS generation, in acute inflammation. In a stereospecific and concentration-dependent manner, the PIPP mimetics directly regulated Streptomyces chromofuscus phospholipase D (sPLD) action. The IC(50) for a (Z)-isomer of endogenous presqualene diphosphate (PSDP) was 100 nM. Structure-activity relationships were also determined for PIPP mimetic inhibition of recombinant human PLD1b, a prominent isoform in human leukocytes. The PIPP mimetic rank order for PLD1b inhibition differed from sPLD, although the (Z)-PSDP isomer remained the most potent PIPP mimetic for inhibition of both enzymes. Truncation of PLD1b to its catalytic core uncovered potential regulatory roles for both PSDP's isoprenoid and diphosphate moieties. The (Z)-PSDP isomer reduced ROS production by activated human leukocytes and decreased murine neutrophil accumulation (65.6%) and ROS production (38.5%) in vivo during zymosan A-initiated peritonitis. When administered intraperitoneally 2 h after zymosan A, the (Z)-PSDP isomer decreased in vivo neutrophil accumulation (72.5%) and ROS generation (74.4%) 6 h later in peritoneal exudates. Together, these results provide new means to protect and control unchecked inflammatory responses that characterize many human diseases. [ABSTRACT FROM AUTHOR]

Discusses the views of authors Edward Eggleston and Edward Bellamy on a narrative device used during the Gilded Age in the U.S. Information on the novels written by Eggleston and Bellamy; Background on the social problems faced by the country in 1887; Influence of language and literature on the history of the country; Analysis of the novel 'The End of the World' written by Eggleston.

The prevalence of asthma continues to increase and its optimal treatment remains a challenge. Here, we investigated the actions of lipoxin A4 (LXA4) and its leukocyte receptor in pulmonary inflammation using a murine model of asthma. Allergen challenge initiated airway biosynthesis of LXA4 and increased expression of its receptor. Administration of a stable analog of LXA4 blocked both airway hyper-responsiveness and pulmonary inflammation, as shown by decreased leukocytes and mediators, including interleukin-5, interleukin-13, eotaxin, prostanoids and cysteinyl leukotrienes. Moreover, transgenic expression of human LXA4 receptors in murine leukocytes led to significant inhibition of pulmonary inflammation and eicosanoid-initiated eosinophil tissue infiltration. Inhibition of airway hyper-responsiveness and allergic airway inflammation with a stable LXA4 analog highlights a unique counter-regulatory profile for the LXA4 system and its leukocyte receptor in airway responses. Moreover, our findings suggest that lipoxin and related pathways offer novel multi-pronged therapeutic approaches for human asthma. [ABSTRACT FROM AUTHOR]

Leukotrienes (LTs) and prostaglandins (PGs) amplify acute inflammation, whereas lipoxins (LXs) have unique anti-inflammatory actions. Temporal analyses of these eicosanoids in clinical and experimental exudates showed early coordinate appearance of LT and PG with polymorphonuclear neutrophil (PMN) recruitment. This was followed by LX biosynthesis, which was concurrent with spontaneous resolution. Human peripheral blood PMNs exposed to PGE2 (as in exudates) switched eicosanoid biosynthesis from predominantly LTB4 and 5-lipoxygenase (5-LO)?initiated pathways to LXA4, a 15-LO product that “stopped” PMN infiltration. These results indicate that first-phase eicosanoids promote a shift to anti-inflammatory lipids: functionally distinct lipid-mediator profiles switch during acute exudate formation to “reprogram” the exudate PMNs to promote resolution. [ABSTRACT FROM AUTHOR]

In this article, the author opines on the management of the dislocated knees with multiple ligament injuries and detection of an arterial lesion in association with a peroneal nerve injury and the controversies related to the knee dislocation. Topics discussed include vascular assessment and treatment, peroneal nerve injury treatment and outcomes, and the role of stress radiographs to assess ligament instability.

Secreted deoxyribonucleases (DNases), such as DNase-I and DNase-IL3, degrade extracellular DNA, and endogenous DNases have roles in resolving airway inflammation and guarding against autoimmune responses to nucleotides. Subsets of patients with asthma have high airway DNA levels, but information about DNase activity in health and in asthma is lacking. To characterize DNase activity in health and in asthma, we developed a novel kinetic assay using a Taqman probe sequence that is quickly cleaved by DNase-I to produce a large product signal. We used this kinetic assay to measure DNase activity in sputum from participants in the Severe Asthma Research Program (SARP)-3 (n = 439) and from healthy controls (n = 89). We found that DNase activity was lower than normal in asthma [78.7 relative fluorescence units (RFU)/min vs. 120.4 RFU/min, P < 0.0001]. Compared to patients with asthma with sputum DNase activity in the upper tertile activity levels, those in the lower tertile of sputum DNase activity were characterized clinically by more severe disease and pathologically by airway eosinophilia and airway mucus plugging. Carbamylation of DNase-I, a post-translational modification that can be mediated by eosinophil peroxidase, inactivated DNase-I. In summary, a Taqman probe-based DNase activity assay uncovers low DNase activity in the asthma airway that is associated with more severe disease and airway mucus plugging and may be caused, at least in part, by eosinophil-mediated carbamylation. NEW & NOTEWORTHY We developed a new DNase assay and used it to show that DNase activity is impaired in asthma airways. [ABSTRACT FROM AUTHOR]

Describes research which found a new intracellular lipid signal that regulates oxygen-radical formation of neutrophils. Generation of lipids in leukocyte membrane remodeling; Screening of neutrophil-derived extracts; Structural analysis of biologically active fractions; Activation of neutrophil receptors; Preparation of presqualene diphosphate (PSDP) and presqualene monophosphate (PSMP); Role of PSDP. INSET: Methods..

An introduction is presented in which the editor discusses various reports within the issue on topics including hip arthroscopy, multimodal analgesia for hip arthroscopic procedures, and diagnosing and managing conditions about the hip.

The article focuses on the asthma susceptibility and sphingolipids linked to airway hyperreactivity in case of asthma. It describes the risk alleles associated with asthma-susceptibility in both children and adults and these risk alleles reside on a common haplotype that harbors three genes encoding such as ORMDL3. It informs that the ORMDL3 protein is expressed in airway epithelium and having major role in sphingolipid metabolism linked to airway hyperreactivity.

The author ponders on the need for early reconstruction for all anterior cruciate ligament (ACL) tears in relation to a study by R. B. Frobell and colleagues. The researchers suggest structured rehabilitation to avoid ACL reconstruction in 50 percent of cases. The presence of articular-cartilage is identified as the most important predictor of the long-term outcome in such cases. The author points out that there is no single treatment strategy for all ACL injuries.

Discusses the significance of the success of prostaglandin (PG) E[sub 2] in structure-function on structure-based therapeutics. Classification of PG; Tissue- and cell type-selective actions of PGE[sub 2]; Impact of PGE[sub 2] actions on designer drug researchers; Popularity of PGE[sub 2] among scientists.

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D- mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long- term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3- encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long- term prevention of asthma and other autoimmune disorders. [ABSTRACT FROM AUTHOR]

Introduction: Previous bronchoalveolar lavage fluid (BALF) proteomic analysis has evaluated limited numbers of subjects for only a few proteins of interest, which may differ between asthma and normal controls. Our objective was to examine a more comprehensive inflammatory biomarker panel in quantitative proteomic analysis for a large asthma cohort to identify molecular phenotypes distinguishing severe from nonsevere asthma. Methods: Bronchoalveolar lavage fluid from 48 severe and 77 nonsevere adult asthma subjects were assessed for 75 inflammatory proteins, normalized to BALF total protein concentration. Validation of BALF differences was sought through equivalent protein analysis of autologous sputum. Subjects' data, stratified by asthma severity, were analysed by standard statistical tests, principal component analysis and 5 machine learning algorithms. Results: The severe group had lower lung function and greater health care utilization. Significantly increased BALF proteins for severe asthma compared to nonsevere asthma were fibroblast growth factor 2 (FGF2), TGFα, IL1Ra, IL2, IL4, CCL8, CCL13 and CXCL7 and significantly decreased were platelet‐derived growth factor a‐a dimer (PDGFaa), vascular endothelial growth factor (VEGF), interleukin 5 (IL5), CCL17, CCL22, CXCL9 and CXCL10. Four protein differences were replicated in sputum. FGF2, PDGFaa and CXCL7 were independently identified by 5 machine learning algorithms as the most important variables for discriminating severe and nonsevere asthma. Increased and decreased proteins identified for the severe cluster showed significant protein–protein interactions for chemokine and cytokine signalling, growth factor activity, and eosinophil and neutrophil chemotaxis differing between subjects with severe and nonsevere asthma. Conclusion: These inflammatory protein results confirm altered airway remodelling and cytokine/chemokine activity recruiting leukocytes into the airways of severe compared to nonsevere asthma as important processes even in stable status. [ABSTRACT FROM AUTHOR]

Background: Hip arthroscopy is rapidly advancing, with positive published outcomes at short- and midterm follow-up; however, available long-term data remain limited. Purpose: To evaluate outcomes of primary hip arthroscopy at a minimum 10-year follow-up at 2 academic centers by describing patient-reported outcomes and determining reoperation and total hip arthroplasty (THA) rates. Study Design: Case series; Level of evidence, 4. Methods: Patients with primary hip arthroscopy performed between January 1988 and April 2013 at 2 academic centers were evaluated for postoperative patient-reported outcomes—including the visual analog scale, Tegner Activity Scale score, Hip Outcome Score Activities of Daily Living and Sport Specific subscales, modified Harris Hip Score, Nonarthritic Hip Score, 12-item International Hip Outcome Tool, surgery satisfaction, and reoperations. Results: A total of 294 patients undergoing primary hip arthroscopy (age, 40 ± 14 years; 66% women; body mass index, 27 ± 6) were followed for 12 ± 3 years (range, 10-24 years) postoperatively. Labral debridement and repair were performed in 41% and 59% of patients, respectively. Of all patients who underwent interportal capsulotomy, 2% were extended to a T-capsulotomy, and 11% underwent capsular repair. At final follow-up, patients reported a mean visual analog scale at rest of 2 ± 2 and with use of 3 ± 3, a 12-item International Hip Outcome Tool of 68 ± 27, a Nonarthritic Hip Score of 81 ± 18, a modified Harris Hip Score of 79 ± 17, and a Hip Outcome Score Activities of Daily Living of 82 ± 19 and Sport Specific subscale of 74 ± 25. The mean surgical satisfaction was 8.4 ± 2.4 on a 10-point scale, with 10 representing the highest level of satisfaction. In total, 96 hips (33%) underwent reoperation—including 65 hips (22%) converting to THA. THA risk factors included older age, higher body mass index, lower lateral center-edge angle, larger alpha angle, higher preoperative Tönnis grade, as well as labral debridement and capsular nonrepair (P ≤.039). Patients undergoing combined labral and capsular repair demonstrated a THA conversion rate of 3% compared with 31% for patients undergoing combined labral debridement and capsular nonrepair (P =.006). Labral repair trended toward increased 10-year THA-free survival (84% vs 77%; P =.085), while capsular repair demonstrated significantly increased 10-year THA-free survival (97% vs 79%; P =.033). Conclusion: At a minimum 10-year follow-up, patients undergoing primary hip arthroscopy demonstrated high satisfaction and acceptable outcome scores. In total, 33% of patients underwent reoperation—including 22% who underwent THA. Conversion to THA was associated with patient factors including older age, higher Tönnis grade, and potentially modifiable surgical factors such as labral debridement and capsular nonrepair. [ABSTRACT FROM AUTHOR]

This article, published in the journal Allergy, discusses the role of a specialized pro-resolving mediator called Resolvin D2 (RvD2) in regulating type 2 inflammatory responses and promoting the resolution of allergic inflammation in mice. The study found that RvD2 decreased airway inflammation, eosinophil accumulation, and bronchial epithelial mucous cell metaplasia in mice with allergic inflammation. RvD2 also reduced airway hyperresponsiveness and levels of pro-inflammatory mediators. The findings suggest that RvD2 may have potential therapeutic benefits for treating asthma and other allergic diseases. [Extracted from the article]

Purpose: Few studies have evaluated the role of hip arthroscopy in patients with coxa profunda. The purposes of this study are to (1) report functional hip outcomes after arthroscopic treatment of patients with femoroacetabular impingement (FAI) associated with radiographic coxa profunda and (2) evaluate factors associated with poor hip function at minimum 2 years following surgery in this specific cohort.Methods: This retrospective review included patients with radiographic sign of coxa profunda who underwent hip arthroscopy to treat FAI. Preoperative and post-operative radiographs were reviewed to determine changes in lateral centre-edge angle (CEA), the presence and correction of Cam deformity, and Tönnis grade of osteoarthritis. Hip functional scores, including modified Harris Hip Score, Hip Outcome Score, and IHOT score, were obtained at a minimum of 2 years following surgery.Results: The study cohort included 46 patients with a mean preoperative CEA of 39.9 (±2.4)° which decreased to a mean of 30.8 (±1.8)° post-operatively. At a mean follow-up of 2.5 years (±0.5), the mean mHHS and IHOT scores were 79.5 (±20.2) and of 69.7 (±28.3), respectively. Increased preoperative (p = 0.02) and post-operative (p = 0.001) Tönnis Osteoarthritis Grade was associated with a lower mHHS.Conclusions: Patients with coxa profunda can achieve similar functional scores to more traditional FAI cohorts after arthroscopic treatment. Baseline osteoarthritis is predictive of lower hip function after hip arthroscopy. This study demonstrates that patients with global over-coverage can benefit from hip arthroscopy and may influence surgeons to treat these patients with less invasive arthroscopic techniques which avoid the morbidity of open surgical procedures.Level Of Evidence: Retrospective case series, Level IV. [ABSTRACT FROM AUTHOR]

The author comments on the article ''How Useful is MRI in Diagnosing Isolated Bundle ACL Injuries?'' It mentions that the authors of the article reported the accuracy of magnetic resonance imaging (MRI) for diagnosis of anterior cruciate ligament (ACL) injuries was 25-53 percent. It also mentions that the authors reported that seven percent of the patients during arthroscopy had an intact isolated anteromedial or posterolateral bundle and the diagnostic accuracy was 83 percent.

Background: Meniscal allograft transplantation (MAT) is an accepted and effective treatment option in the context of unsalvageable menisci, particularly in young and active patients. It has been shown to reduce pain and improve knee function in previously symptomatic patients. However, there is still limited knowledge about the long-term survival rates of allografts, the durability of clinical results, and the influence of patient-specific parameters, such as leg alignment, tibial slope, and preoperative International Cartilage Regeneration & Joint Preservation Society (ICRS) grade. Purpose: To determine (1) the long-term clinical success rate after MAT with bony fixation in a large, single-center cohort of consecutive patients, and (2) if patient-specific and procedural variables influence the clinical, anatomic, and subjective outcomes and risk of failure. Study Design: Case-control study; Level of evidence, 3. Methods: Data on 185 consecutive knees undergoing MAT in a single institution were prospectively collected and screened for inclusion in this study. The minimum follow-up time was 2 years. Radiographic variables (ICRS grade and Kellgren-Lawrence grade) were assessed preoperatively and at follow-up. Subjective patient-reported outcome measures (PROMs) (Lysholm score, Knee injury and Osteoarthritis Outcome Score [KOOS] including subscores, International Knee Documentation Committee [IKDC] score, and visual analog scale [VAS] score) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery due to graft failure or conversion to total knee arthroplasty. Anatomic failure was considered a tear covering >20% of the allograft, any peripheral tear, and unstable peripheral fixation leading to dislocation of the graft. Subjective failure was defined as Lysholm score ≤65. Preoperative tibial slope and leg alignment were assessed. Survival analyses were performed using the Kaplan-Meier estimate. Univariate and multivariate analyses were performed to determine risk factors for clinical and anatomic failure. Results: A total of 157 knees met inclusion criteria. After a mean follow-up time of 7 ± 3.5 years, 127 (80.9%) knees were free of clinical, anatomic, and subjective failure. Fourteen (8.9%) knees experienced clinical failure, 26 (16.6%) knees were identified as having experienced anatomic failure, and 13 (8.3%) patients experienced subjective failure with a reported Lysholm score of ≤65 at a mean follow-up of 7 years. Concurrent osteochondral allograft transplantation was identified as a predictor of both clinical (hazard ratio [HR], 4.55; 95% CI, 1.46-14.17; P =.009) and anatomic (HR, 3.05; 95% CI, 1.34-6.92; P =.008) failure. Cartilage damage of ICRS grade 3 or 4 of the index compartment conveyed an increased risk for clinical (HR, 3.41; 95% CI, 1.05-11.01; P =.04) and anatomic (HR, 3.04; 95% CI, 1.31-7.11; P =.01) failure. High-grade cartilage damage preoperatively (HR, 10.67; 95% CI, 1.037-109.768; P =.046), patient age >25 years (HR, 5.44; 95% CI, 0.120-246.070; P =.384), and a body mass index >30 (HR, 2.24; 95% CI, 0.748-6.705; P =.149) were associated with subjective failure. PROMs including KOOS and IKDC were significantly improved at final follow-up compared with preoperative scores across all measurements (P <.005). Conclusion: MAT showed good to excellent clinical results at a mean follow-up of 7 years. Low ICRS lesion grade was associated with a higher clinical and anatomic survival rate. Patients with concurrent OCA transplantation are at a higher risk of clinical and anatomic failure, but still report significantly improved PROMs. These results suggest that MAT has a lasting beneficial effect both in isolation and in complex cases with ≥1 concurrent procedures. [ABSTRACT FROM AUTHOR]

Background: Historically, symptomatic hip labral lesions were treated with arthroscopic debridement. Hip labral repair has become the standard treatment for labral pathology; however, to date, there are limited long-term studies regarding the outcomes of isolated labral debridement. Purpose: To (1) evaluate the long-term patient-reported outcomes of isolated labral debridement, (2) report reoperation and arthroplasty rates, and (3) identify risk factors contributing to reoperation or poor clinical outcomes. Study Design: Case series; Level of evidence, 4 Methods: A retrospective review of a prospectively generated cohort of 59 hips in 57 patients from 1996 to 2010 who underwent hip arthroscopy with labral debridement was performed. Only patients with Tönnis grade <3 were included. Additionally, given the time period analyzed, resection of cam morphology was not performed, and the interportal capsulotomy was not repaired. The pre- and postoperative modified Harris Hip Score; Hip Outcome Score (HOS)-Activities of Daily Living and -Sports scores; and reoperation, conversion to total hip arthroplasty, and risk factors were analyzed. Results: In total, 48 hips in 47 patients (14 men, 33 women; mean age, 48.0 ± 12.9 years) met inclusion criteria and were followed for a mean of 17 ± 3 years (range, 13-27 years). The mean preoperative Tönnis grade was 1.3 ± 0.6 (range, 0-2), the mean chondral acetabular International Cartilage Regeneration & Joint Preservation Society (ICRS) grade was 1.7 ± 1.6 (range, 0-4), the mean chondral femoral ICRS grade was 0.9 ± 1.4, and the mean acetabular labral articular cartilage grade was 2.5 ± 1.2 (range, 0-4). At the final follow-up, mean the modified Harris Hip Score, HOS-Activities of Daily Living score, and HOS-Sports score were 82.2 ± 16.6, 81.9 ± 20.5, and 82.2 ± 20.5, respectively. Nineteen hips underwent subsequent reoperation at a mean of 5.5 ± 6.2 years (range, 0.5-21.2 years) postoperatively, including 16 hips (33% overall) being converted to total hip arthroplasty. Higher acetabular ICRS chondral grades at the time of surgery were observed in patients who went on to subsequent surgery compared with those who did not (2.3 ± 1.6 vs 1.1 ± 1.5; P =.02). In reoperation-free hips, Tönnis grade demonstrated a trend of increasing over time (1.4 preoperatively vs 1.7 at radiographic follow-up; P =.08). At the final follow-up, 19 hips (40%) had undergone reoperation, and 5 additional hips (10%) were rated as "abnormal" or "severely abnormal" in function, resulting in an overall clinical failure rate of 50%. Conclusion: Isolated labral debridement was found to result in high rates of failure and reoperation, with a third of patients being converted to arthroplasty and half of patients meeting criteria for reoperation or clinical failure. Of note, for patients remaining reoperation-free, satisfactory outcome scores were observed. [ABSTRACT FROM AUTHOR]

The author comments on an article "Does Sequence of Graft Tensioning Affect Outcomes in Combined Anterior and Posterior Cruciate Ligament Reconstructions?" by Se-Won Lee and colleagues which appeared in the January 2015 issue of the periodical. Topics discussed include the variability of multiligament knee injuries, use of radiographs and functional scores and anterior cruciate ligament (ACL) graft fixation. Other topics include damage of collateral ligament.

Purpose: Identifying predictive factors for all-cause reoperation after anterior cruciate ligament reconstruction could inform clinical decision making and improve risk mitigation. The primary purposes of this study are to (1) determine the incidence of all-cause reoperation after anterior cruciate ligament reconstruction, (2) identify predictors of reoperation after anterior cruciate ligament reconstruction using machine learning methodology, and (3) compare the predictive capacity of the machine learning methods to that of traditional logistic regression. Methods: A longitudinal geographical database was utilized to identify patients with a diagnosis of new anterior cruciate ligament injury. Eight machine learning models were appraised on their ability to predict all-cause reoperation after anterior cruciate ligament reconstruction. Model performance was evaluated via area under the receiver operating characteristics curve. To explore modeling interpretability and radiomic feature influence on the predictions, we utilized a game-theory-based method through SHapley Additive exPlanations. Results: A total of 1400 patients underwent anterior cruciate ligament reconstruction with a mean postoperative follow-up of 9 years. Two-hundred and eighteen (16%) patients experienced a reoperation after anterior cruciate ligament reconstruction, of which 6% of these were revision ACL reconstruction. SHapley Additive exPlanations plots identified the following risk factors as predictive for all-cause reoperation: diagnosis of systemic inflammatory disease, distal tear location, concomitant medial collateral ligament repair, higher visual analog scale pain score prior to surgery, hamstring autograft, tibial fixation via radial expansion device, younger age at initial injury, and concomitant meniscal repair. Pertinent negatives, when compared to previous studies, included sex and timing of surgery. XGBoost was the best-performing model (area under the receiver operating characteristics curve of 0.77) and outperformed logistic regression in this regard. Conclusions: All-cause reoperation after anterior cruciate ligament reconstruction occurred at a rate of 16%. Machine learning models outperformed traditional statistics and identified diagnosis of systemic inflammatory disease, distal tear location, concomitant medial collateral ligament repair, higher visual analog scale pain score prior to surgery, hamstring autograft, tibial fixation via radial expansion device, younger age at initial injury, and concomitant meniscal repair as predictive risk factors for reoperation. Pertinent negatives, when compared to previous studies, included sex and timing of surgery. These models will allow surgeons to tabulate individualized risk for future reoperation for patients undergoing anterior cruciate ligament reconstruction. Level of evidence: III. [ABSTRACT FROM AUTHOR]

Subphenotypes of asthma may be determined by age onset and atopic status. We sought to characterize early or late onset atopic asthma with fungal or non-fungal sensitization (AAFS or AANFS) and non-atopic asthma (NAA) in children and adults in the Severe Asthma Research Program (SARP). SARP is an ongoing project involving well-phenotyped patients with mild to severe asthma. Phenotypic comparisons were performed using Kruskal-Wallis or chi-square test. Genetic association analyses were performed using logistic or linear regression. Airway hyper-responsiveness, total serum IgE levels, and T2 biomarkers showed an increasing trend from NAA to AANFS and then to AAFS. Children and adults with early onset asthma had greater % of AAFS than adults with late onset asthma (46% and 40% vs. 32%; P < 0.00001). In children, AAFS and AANFS had lower % predicted FEV1 (86% and 91% vs. 97%) and greater % of patients with severe asthma than NAA (61% and 59% vs. 43%). In adults with early or late onset asthma, NAA had greater % of patients with severe asthma than AANFS and AAFS (61% vs. 40% and 37% or 56% vs. 44% and 49%). The G allele of rs2872507 in GSDMB had higher frequency in AAFS than AANFS and NAA (0.63 vs. 0.55 and 0.55), and associated with earlier age onset and asthma severity. Early or late onset AAFS, AANFS, and NAA have shared and distinct phenotypic characteristics in children and adults. AAFS is a complex disorder involving genetic susceptibility and environmental factors. [ABSTRACT FROM AUTHOR]

Genome-wide association studies (GWASs) have identified single nucleotide polymorphisms (SNPs) in chr11p15.5 region associated with asthma and idiopathic interstitial pneumonias (IIPs). We sought to identify functional genes for asthma by combining SNPs and mRNA expression in bronchial epithelial cells (BEC) in the Severe Asthma Research Program (SARP). Correlation analyses of mRNA expression of six candidate genes (AP2A2, MUC6, MUC2, MUC5AC, MUC5B, and TOLLIP) and asthma phenotypes were performed in the longitudinal cohort (n = 156) with RNAseq in BEC, and replicated in the cross-sectional cohort (n = 155). eQTL (n = 114) and genetic association analysis of asthma severity (426 severe vs. 531 non-severe asthma) were performed, and compared with previously published GWASs of IIPs and asthma. Higher expression of AP2A2 and MUC5AC and lower expression of MUC5B in BEC were correlated with asthma, asthma exacerbations, and T2 biomarkers (P < 0.01). SNPs associated with asthma and IIPs in previous GWASs were eQTL SNPs for MUC5AC, MUC5B, or TOLLIP, however, they were not in strong linkage disequilibrium. The risk alleles for asthma or protective alleles for IIPs were associated with higher expression of MUC5AC and lower expression of MUC5B. rs11603634, rs12788104, and rs28415845 associated with moderate-to-severe asthma or adult onset asthma in previous GWASs were not associated with asthma severity (P > 0.8). SNPs associated with asthma in chr11p15.5 region are not associated with asthma severity neither with IIPs. Higher expression of MUC5AC and lower expression of MUC5B are risk for asthma but protective for IIPs. [ABSTRACT FROM AUTHOR]