| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Meredith, S. J., et al.
(författare)
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Return to sport after anterior cruciate ligament injury: Panther Symposium ACL Injury Return to Sport Consensus Group
- 2020
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 28, s. 2403-2414
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Tidskriftsartikel (refereegranskat)abstract
- Purpose A precise and consistent definition of return to sport (RTS) after anterior cruciate ligament (ACL) injury is lacking, and there is controversy surrounding the process of returning patients to sports and their previous activity level. The aim of the Panther Symposium ACL Injury RTS Consensus Group was to provide a clear definition of RTS and description of the RTS continuum, as well as to provide clinical guidance on RTS testing and decision-making. Methods An international, multidisciplinary group of ACL experts convened as part of a consensus meeting. Consensus statements were developed using a modified Delphi method. Literature review was performed to report the supporting evidence. Results Key points include that RTS is characterized by achievement of the pre-injury level of sport and involves a criteria-based progression from return to participation to return to sport, and ultimately return to performance. Purely time-based RTS decision-making should be abandoned. Progression occurs along a RTS continuum with decision-making by a multidisciplinary group that incorporates objective physical examination data and validated and peer-reviewed RTS tests, which should involve functional assessment as well as psychological readiness. Consideration should be given to biological healing, contextual factors and concomitant injuries. Conclusion The resultant consensus statements and scientific rationale aim to inform the reader of the complex process of RTS after ACL injury that occurs along a dynamic continuum. Research is needed to determine the ideal RTS test battery, the best implementation of psychological readiness testing and methods for the biologic assessment of healing and recovery.
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| 3. |
- Meredith, S. J., et al.
(författare)
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Return to sport after anterior cruciate ligament injury: Panther Symposium ACL Injury Return to Sport Consensus Group
- 2021
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Ingår i: Journal of Isakos Joint Disorders & Orthopaedic Sports Medicine. - : Elsevier BV. - 2059-7754. ; 6:3, s. 138-146
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Tidskriftsartikel (refereegranskat)abstract
- Objectives A precise and consistent definition of return to sport (RTS) after anterior cruciate ligament (ACL) injury is lacking, and there is controversy surrounding the process of returning patients to sports and their previous activity level. The aim of the Panther Symposium ACL Injury RTS Consensus Group was to provide a clear definition of RTS after ACL injury and description of the RTS continuum, as well as provide clinical guidance on RTS testing and decision-making. Methods An international, multidisciplinary group of ACL experts convened as part of a consensus meeting. Consensus statements were developed using a modified Delphi method. Literature review was performed to report the supporting evidence. Results Key points include that RTS is characterised by achievement of the preinjury level of sport and involves a criteria-based progression from return to participation to RTS, and ultimately return to performance. Purely time-based RTS decision-making should be abandoned. Progression occurs along an RTS continuum with decision-making by a multidisciplinary group that incorporates objective physical examination data and validated and peer-reviewed RTS tests, which should involve functional assessment as well as psychological readiness. Consideration should be given to biological healing, contextual factors and concomitant injuries. Conclusion The resultant consensus statements and scientific rationale aim to inform the reader of the complex process of RTS after ACL injury that occurs along a dynamic continuum. Research is needed to determine the ideal RTS test battery, the best implementation of psychological readiness testing and methods for the biological assessment of healing and recovery.
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| 4. |
- Ozbek, E. A., et al.
(författare)
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Failure Rates and Complications After Multiple-Revision ACL Reconstruction: Comparison of the Over-the-Top and Transportal Drilling Techniques
- 2023
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Ingår i: Orthopaedic Journal of Sports Medicine (OJSM). - 2325-9671. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Background:Multiple-revision anterior cruciate ligament reconstruction (ACLR) presents several technical challenges, often due to residual hardware, tunnel widening, malposition, or staged surgeries. Purpose:To compare failure and complication rates between the over-the-top (OTT) and transportal drilling (TD) techniques in patients undergoing surgery for failed revision ACLR. Study Design:Cohort study; Level of evidence, 3. Methods:The medical records of patients with at least 2 revision ACLRs using either the OTT or TD technique were reviewed retrospectively. Data on patient demographics, graft characteristics, number of revisions, concomitant procedures, complications, and failures were collected. Between-group comparisons of continuous and categorical variables were conducted with the independent-samples t test and the Fisher exact or chi-square test, respectively. Results:A total of 101 patients undergoing multiple-revision ACLR with OTT (n = 37, 37%) and TD (n = 64, 63%) techniques were included for analysis. The mean follow-up time was 60 months (range, 12-196 months). There were no significant differences in age, sex, body mass index, laterality, or follow-up length between groups (P > .05). Allograft was the graft used most frequently (n = 64; 67.3%) with no significant differences between groups in graft diameter (P > .05). There were no statistically significant differences between groups regarding rate of concurrent medial and lateral meniscus, cartilage, or lateral extra-articular procedures (P > .05). There was also no significant66 between-group difference in complication rate (OTT: n = 2 [5.4%]; TD: n = 8 [13%]) or graft failure rate (OTT: n = 4 [11%]; TD: n = 14 [22%]) (P > .05 for both). Conclusion:The results of this study showed notably high failure and complication rates in challenging multiple-revision ACLR. Complication and failure rates were similar between techniques, demonstrating that the OTT technique is a valuable alternative that can be used in a revision ACLR, particularly as a single-stage approach when the single-stage TD technique is not possible.
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| 5. |
- Setliff, J. C., et al.
(författare)
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Anterior cruciate ligament reconstruction with all-soft tissue quadriceps tendon versus quadriceps tendon with bone block
- 2022
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Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 31:7, s. 2844-2851
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to evaluate whether there was a difference in clinical outcomes between patients who underwent primary ACL reconstruction (ACLR) with all-soft tissue quadriceps tendon (sQT) autograft versus QT with bone block (bQT). Methods: A retrospective cohort study of 708 patients who underwent QT ACLR was conducted. Primary ACLR patients with at least 1year of follow-up were identified and those who received sQT were compared to those who received bQT. Data collection entailed patient demographics, surgical variables, patient reported outcomes (PROs), knee stability testing, and complications. The primary outcome of interest was International Knee Documentation Committee (IKDC) score, reported as mean score, pre- and postoperative difference, and number who met minimum clinically important difference (MCID). Secondary outcomes included Lachman and pivot shift grade, other patient reported outcomes (PROs), complication rates, and return to sport (RTS). Results: A total of 195 patients (147 sQT, 48 bQT) who underwent primary QT ACLR met criteria for analysis, with mean follow-up of 17.0 ± 7.9months. No difference was detected between cohorts with respect to postoperative IKDC score (sQT: n = 120, 81.0 ± 18.9, bQT: n = 10, 80.9 ± 20.4, n.s.), proportion of patients who met MCID (sQT: 68/78 [87%], bQT: 6/7 [86%], n.s.), or results of stability testing. In the sQT cohort, 86% (106/123) of athletes achieved full RTS, compared to 85% (34/40) in the bQT cohort (n.s.). Time to RTS was less than a year in both cohorts (sQT: 10.5 ± 3.8months [n = 106], bQT: 11.1 ± 3.9months [n = 31], n.s.). Graft rupture occurred in 7 (5%) sQT patients and 3 (6%) bQT patients (n.s.), and all clinical failures were due to graft rupture (n.s.). No differences were detected for rates of postoperative complications. Conclusion: No differences in clinical outcomes were detected between patients who underwent primary ACLR with sQT autograft versus bQT autograft. Currently, the decision to employ sQT or bQT is largely determined by surgeon preference. This study demonstrates excellent outcomes with both preparations and supports the use of either graft type at the discretion of the treating surgeon. Level of evidence: III.
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| 6. |
- Brem, Jürgen, et al.
(författare)
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Imitation of β-lactam binding enables broad-spectrum metallo-β-lactamase inhibitors
- 2022
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Ingår i: Nature Chemistry. - : Springer Nature. - 1755-4330 .- 1755-4349. ; 14:1, s. 15-24
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Tidskriftsartikel (refereegranskat)abstract
- Carbapenems are vital antibiotics, but their efficacy is increasingly compromised by metallo-β-lactamases (MBLs). Here we report the discovery and optimization of potent broad-spectrum MBL inhibitors. A high-throughput screen for NDM-1 inhibitors identified indole-2-carboxylates (InCs) as potential β-lactamase stable β-lactam mimics. Subsequent structure-activity relationship studies revealed InCs as a new class of potent MBL inhibitor, active against all MBL classes of major clinical relevance. Crystallographic studies revealed a binding mode of the InCs to MBLs that, in some regards, mimics that predicted for intact carbapenems, including with respect to maintenance of the Zn(II)-bound hydroxyl, and in other regards mimics binding observed in MBL-carbapenem product complexes. InCs restore carbapenem activity against multiple drug-resistant Gram-negative bacteria and have a low frequency of resistance. InCs also have a good in vivo safety profile, and when combined with meropenem show a strong in vivo efficacy in peritonitis and thigh mouse infection models.
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| 7. |
- Hughes, Jonathan D., et al.
(författare)
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More anterior placement of femoral tunnel position in ACL-R is associated with postoperative meniscus tears
- 2023
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Ingår i: Journal of Experimental Orthopaedics. - 2197-1153. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe purpose of this study was to investigate the relationship between tunnel position in ACL reconstruction (ACL-R) and postoperative meniscus tears.MethodsThis was a single institution, case-control study of 170 patients status-post ACL-R (2010-2019) separated into two matched groups (sex, age, BMI, graft type). Group 1-symptomatic, operative meniscus tears (both de novo and recurrent) after ACL-R. Group 2-no postoperative meniscus tears. Femoral and tibial tunnel positions were measured by 2 authors via lateral knee radiographs that were used to measure two ratios (a/t and b/h). Ratio a/t was defined as distance from the tunnel center to dorsal most subchondral contour of the lateral femoral condyle (a) divided by total sagittal diameter of the lateral condyle along Blumensaat's line (t). The ratio b/h was defined as distance between the tunnel and Blumensaat's line (b) divided by maximum intercondylar notch height (h). Wilcoxon sign-ranks paired test was used to compare measurements between groups (alpha set at p < 0.05).ResultsGroup 1 had average follow up of 45 months and Group 2 had average follow up of 22 months. There were no significant demographic differences between Groups 1 and 2. Group 1-a/t was 32.0% (& PLUSMN; 10.2), which was significantly more anterior than group 2, 29.3% (& PLUSMN; 7.3; p < 0.05). There was no difference in average femoral tunnel ratio b/h or tibial tunnel placement between groups.ConclusionsA relationship exists between more anterior/less anatomic femoral tunnel position and the presence of recurrent or de novo, operative meniscus tears after ACL-R. Surgeons performing ACL-R should strive for recreation of native anatomy via proper tunnel placement to maximize postoperative outcomes.
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| 8. |
- Meredith, Sean J., et al.
(författare)
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Return to Sport After Anterior Cruciate Ligament Injury: Panther Symposium ACL Injury Return to Sport Consensus Group
- 2020
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Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Background: A precise and consistent definition of return to sport (RTS) after anterior cruciate ligament (ACL) injury is lacking, and there is controversy surrounding the process of returning patients to sport and their previous activity level. Purpose: The aim of the Panther Symposium ACL Injury Return to Sport Consensus Group was to provide a clear definition of RTS after ACL injury and a description of the RTS continuum as well as provide clinical guidance on RTS testing and decision-making. Study Design: Consensus statement. Methods: An international, multidisciplinary group of ACL experts convened as part of a consensus meeting. Consensus statements were developed using a modified Delphi method. Literature review was performed to report the supporting evidence. Results: Key points include that RTS is characterized by achievement of the preinjury level of sport and involves a criteria-based progression from return to participation to RTS and, ultimately, return to performance. Purely time-based RTS decision-making should be abandoned. Progression occurs along an RTS continuum, with decision-making by a multidisciplinary group that incorporates objective physical examination data and validated and peer-reviewed RTS tests, which should involve functional assessment as well as psychological readiness. Consideration should be given to biological healing, contextual factors, and concomitant injuries. Conclusion: The resultant consensus statements and scientific rationale aim to inform the reader of the complex process of RTS after ACL injury that occurs along a dynamic continuum. Research is needed to determine the ideal RTS test battery, the best implementation of psychological readiness testing, and methods for the biological assessment of healing and recovery.
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| 9. |
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| 10. |
- Svantesson, Eleonor, et al.
(författare)
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Clinical Outcomes After Anterior Cruciate Ligament Injury: Panther Symposium ACL Injury Clinical Outcomes Consensus Group.
- 2020
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Ingår i: Orthopaedic journal of sports medicine. - 2325-9671. ; 8:7
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Tidskriftsartikel (refereegranskat)abstract
- A stringent outcome assessment is a key aspect of establishing evidence-based clinical guidelines for anterior cruciate ligament (ACL) injury treatment. To establish a standardized assessment of clinical outcome after ACL treatment, a consensus meeting including a multidisciplinary group of ACL experts was held at the ACL Consensus Meeting Panther Symposium, Pittsburgh, Pennsylvania, USA, in June 2019. The aim was to establish a consensus on what data should be reported when conducting an ACL outcome study, what specific outcome measurements should be used, and at what follow-up time those outcomes should be assessed. The group reached consensus on 9 statements by using a modified Delphi method. In general, outcomes after ACL treatment can be divided into 4 robust categories: early adverse events, patient-reported outcomes (PROs), ACL graft failure/recurrent ligament disruption, and clinical measures of knee function and structure. A comprehensive assessment after ACL treatment should aim to provide a complete overview of the treatment result, optimally including the various aspects of outcome categories. For most research questions, a minimum follow-up of 2 years with an optimal follow-up rate of 80% is necessary to achieve a comprehensive assessment. This should include clinical examination, any sustained reinjuries, validated knee-specific PROs, and health-related quality of life questionnaires. In the midterm to long-term follow-up, the presence of osteoarthritis should be evaluated. This consensus paper provides practical guidelines for how the aforementioned entities of outcomes should be reported and suggests the preferred tools for a reliable and valid assessment of outcome after ACL treatment.
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| 11. |
- Byrne, K. J., et al.
(författare)
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Non-anatomic tunnel position increases the risk of revision anterior cruciate ligament reconstruction
- 2022
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; :30, s. 1388-1395
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Anterior cruciate ligament (ACL) graft failure is a complication that may require revision ACL reconstruction (ACL-R). Non-anatomic placement of the femoral tunnel is thought to be a frequent cause of graft failure; however, there is a lack of evidence to support this belief. The purpose of this study was to determine if non-anatomic femoral tunnel placement is associated with increased risk of revision ACL-R. Methods After screening all 315 consecutive patients who underwent primary single-bundle ACL-R by a single senior orthopedic surgeon between January 2012 and January 2017, 58 patients were found to have both strict lateral radiographs and a minimum of 24 months follow-up without revision. From a group of 456 consecutive revision ACL-R, patients were screened for strictly lateral radiographs and 59 patients were included in the revision group. Femoral tunnel placement for each patient was determined using a strict lateral radiograph taken after the primary ACL-R using the quadrant method. The center of the femoral tunnel was measured in both the posterior-anterior (PA) and proximal-distal (PD) dimensions and represented as a percentage of the total distance (normal center of anatomic footprint: PA 25% and PD 29%). Results In the PA dimension, the revision group had significantly more anterior femoral tunnel placement compared with the primary group (38% +/- 11% vs. 28% +/- 6%, p < 0.01). Among patients who underwent revision; those with non-traumatic chronic failure had statistically significant more anterior femoral tunnel placement than those who experienced traumatic failure (41% +/- 13% vs. 35% +/- 8%, p < 0.03). In the PD dimension, the revision group had significantly more proximal femoral tunnel placement compared with the primary group (30% +/- 9% vs 38% +/- 9%, p < 0.01). Conclusion In this retrospective study of 58 patients with successful primary ACL-R compared with 59 patients with failed ACL-R, anterior and proximal (high) femoral tunnels for ACL-R were shown to be independent risk factors for ACL revision surgery. As revision ACL-R is associated with patient- and economic burden, particular attention should be given to achieving an individualized, anatomic primary ACL-R. Surgeons may reduce the risk of revision ACL-R by placing the center of the femoral tunnel within the anatomic ACL footprint.
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| 12. |
- Setliff, J. C., et al.
(författare)
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Harvesting a second graft from the extensor mechanism for revision ACL reconstruction does not delay return of quadriceps function
- 2023
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 31:7, s. 2828-2835
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Tidskriftsartikel (refereegranskat)abstract
- Purpose The purpose of this study was to evaluate whether harvesting a second graft from the ipsilateral extensor mechanism adversely affects clinical outcomes in revision anterior cruciate ligament (ACL) reconstruction. Methods A retrospective review of 34 patients undergoing revision anterior cruciate ligament (ACL) reconstruction with either quadriceps tendon (QT) autograft or bone-tendon-bone (BTB) autograft was conducted. Patients with two grafts (BTB+QT) from the extensor mechanism were matched based on age, laterality, and sex to patients who had primary reconstruction with hamstring (HS) autograft followed by revision with either BTB or QT autograft (HS+QT/BTB). Return of quadriceps function was assessed with time to return to jogging in a standardized rehab protocol or time to regain 80% quadriceps strength. Secondary outcomes included International Knee Documentation Committee (IKDC) and Marx scores at 12-month follow-up and return to sport. Results There were no significant differences in return to jogging or 80% quadriceps strength (HS 149.5 +/- 38.2 days, BTB+QT 131.7 +/- 40.1 days, n.s.), number able to return to sport (HS 62%, BTB+QT 93%, n.s.), months to return to sport (HS 10.6 +/- 1.4, BTB+QT 10.5 +/- 2.3, n.s.), return to pre-injury level of competition (HS 62%, BTB+QT 73%, n.s.), or IKDC (HS 77.2 +/- 16.4, BTB+QT 74.8 +/- 23.9, n.s.) and Marx scores (HS 9.2 +/- 5.3, BTB+QT 8.0 +/- 3.7, n.s.) at one-year follow-up. Conclusion The main finding of the present study was that outcomes for patients who underwent revision ACL reconstruction with a second extensor mechanism autograft were comparable to those seen for patients who underwent revision ACL reconstruction with extensor mechanism autograft after primary ACL reconstruction with hamstring autograft. By better understanding the consequences of harvesting a second graft from the extensor mechanism, surgeons can better decide what graft to use in revision ACL reconstruction.
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