Purpose
In August 2011, orthopaedic surgeons from more than 20 countries attended a summit on anatomic anterior cruciate ligament (ACL) reconstruction. The summit offered a unique opportunity to ...discuss current concepts, approaches, and techniques in the field of ACL reconstruction among leading surgeons in the field.
Methods
Five panels (with 36 panellists) were conducted on key issues in ACL surgery: anatomic ACL reconstruction, rehabilitation and return to activity following anatomic ACL reconstruction, failure after ACL reconstruction, revision anatomic ACL reconstruction, and partial ACL injuries and ACL augmentation. Panellists’ responses were secondarily collected using an online survey.
Results
Thirty-six panellists (35 surgeons and 1 physical therapist) sat on at least one panel. Of the 35 surgeons surveyed, 22 reported performing “anatomic” ACL reconstructions. The preferred graft choice was hamstring tendon autograft (53.1 %) followed by bone-patellar tendon-bone autograft (22.8 %), allograft (13.5 %), and quadriceps tendon autograft (10.6 %). Patients generally returned to play after an average of 6 months, with return to full competition after an average of 8 months. ACL reconstruction “failure” was defined by 12 surgeons as instability and pathological laxity on examination, a need for revision, and/or evidence of tear on magnetic resonance imaging. The average percentage of patients meeting the criteria for “failure” was 8.2 %.
Conclusions
These data summarize the results of five panels on anatomic ACL reconstruction. The most popular graft choice among surgeons for primary ACL reconstructions is hamstring tendon autograft, with allograft being used most frequently employed in revision cases. Nearly half of the surgeons surveyed performed both single- and double-bundle ACL reconstructions depending on certain criteria. Regardless of the technique regularly employed, there was unanimous support among surgeons for the use of “anatomic” reconstructions using bony and soft tissue remnant landmarks.
Level of evidence
V.
Abstract
Recent studies suggest that as the trade wind in the Caribbean Sea weakens from summer to fall, conditions become more favorable for the Loop Current in the Gulf of Mexico to shed an ...anticyclonic ring. This idea originated with observations showing a preference for more eddies from summer through fall, and it was confirmed using multidecadal model experiments. Here, the hypothesis is further tested by studying the dynamics of a specific eddy-shedding event in summer 2011 using a model experiment initialized with observation-assimilated reanalysis and forced by reanalysis wind from NCEP. Eddy shedding in July 2011 is shown to follow the weakening of the trade wind and Yucatan transport in late June. The shedding time is significantly earlier than can be explained based on reduced-gravity Rossby wave dynamics. Altimetry and model data are analyzed to show that empirical orthogonal function modes 1 + 2 dominate the reduced-gravity process, while higher modes contain the coupling of the Loop Current with deep layer underneath. The Loop’s westward expansion at incipient shedding induces a deep cyclonic gyre in the eastern Gulf, embedded within which are small cyclones caused by the baroclinic instability of the strongly sheared current north of the Campeche Bank. The associated deep upwelling and upper-layer divergence from these cyclonic circulations accelerate eddy shedding.
Plasmamembrane small conductance Ca2+-activated K+ (SK) channels were implicated in ventricular arrhythmias in infarcted and failing hearts. Recently, SK channels were detected in the inner ...mitochondria membrane (IMM) (mSK), and their activation protected from acute ischaemia-reperfusion injury by reducing intracellular levels of reactive oxygen species (ROS). We hypothesized that mSK play an important role in regulating mitochondrial function in chronic cardiac diseases. We investigated the role of mSK channels in Ca2+-dependent ventricular arrhythmia using rat model of cardiac hypertrophy induced by banding of the ascending aorta thoracic aortic banding (TAB).
Dual Ca2+ and membrane potential optical mapping of whole hearts derived from TAB rats revealed that membrane-permeable SK enhancer NS309 (2 μM) improved aberrant Ca2+ homeostasis and abolished VT/VF induced by β-adrenergic stimulation. Using whole cell patch-clamp and confocal Ca2+ imaging of cardiomyocytes derived from TAB hearts (TCMs) we found that membrane-permeable SK enhancers NS309 and CyPPA (10 μM) attenuated frequency of spontaneous Ca2+ waves and delayed afterdepolarizations. Furthermore, mSK inhibition enhanced (UCL-1684, 1 μM); while activation reduced mitochondrial ROS production in TCMs measured with MitoSOX. Protein oxidation assays demonstrated that increased oxidation of ryanodine receptors (RyRs) in TCMs was reversed by SK enhancers. Experiments in permeabilized TCMs showed that SK enhancers restored SR Ca2+ content, suggestive of substantial improvement in RyR function.
These data suggest that enhancement of mSK channels in hypertrophic rat hearts protects from Ca2+-dependent arrhythmia and suggest that the protection is mediated via decreased mitochondrial ROS and subsequent decreased oxidation of reactive cysteines in RyR, which ultimately leads to stabilization of RyR-mediated Ca2+ release.
Three independent scientific lines of evidence were sought to determine the nutrient load limits to safeguard the macrophyte community of an intermittently closed and open lake/lagoon (ICOLL): (1) a ...literature review identified nitrogen load thresholds related to the collapse of macrophytes in similar systems in Australia, Europe and elsewhere, (2) an ICOLL expert carried out an assessment based on current local data and on data from 57 Australian coastal lakes and lagoons, and (3) a deterministic coupled hydrodynamic-ecological model was developed and applied to simulate the ecological outcomes of several nutrient loading scenarios. The three lines of evidence converged on well-defined nitrogen load estimates required to avoid the collapse of the macrophyte community. Uncertainties were slightly greater in relation to required phosphorus load limits, but the evidence still helped set a precautionary phosphorus load limit that accounted for these uncertainties. Thus, despite the challenges in setting load limits for complex ecosystems, multiple lines of evidence helped derive robust nutrient load limits for managing the ICOLL to safeguard values associated with a healthy macrophyte community.
Background:
Alpha‐4 integrins facilitate leucocyte migration across vascular endothelium.
Aim:
To assess the safety and efficacy of natalizumab (Antegren), a humanized antibody to alpha‐4 integrin, ...in patients with active ulcerative colitis.
Methods:
Ten patients with active ulcerative colitis, defined by a Powell‐Tuck activity score > 4, received a single 3 mg/kg natalizumab infusion. The primary end‐point was the change in Powell‐Tuck score at 2 weeks post‐infusion.
Results
Significant decreases in the median Powell‐Tuck score were observed at 2 and 4 weeks post‐infusion (7.5 and 6, respectively) compared to the median baseline score (10). Five of 10 patients achieved a good clinical response at 2 weeks and one more patient by 4 weeks, defined by a Powell‐Tuck score of ≤ 5. Significant improvements in quality of life scores were found at week 4. Rescue medication was required by two (20%), three (30%) and eight (80%) patients by weeks 2, 4 and 8, respectively (median, 34 days; range, 8–43 days). One patient remained in remission at 12 weeks. The median C‐reactive protein at 2 weeks (6 mg/L) was lower than that pre‐treatment (16 mg/L).
Conclusions:
A single 3 mg/kg infusion of natalizumab was well tolerated by ulcerative colitis patients. The positive efficacy demonstrated in this study merits further investigation by randomized, placebo‐controlled trials.
•Local Ensemble Transform Kalman Filter (LETKF) is tested in Loop Current.•LETKF and OI skills are rigorously assessed against in situ ADCP’s and satellite.•LETKF captures nonlinear behaviors of eddy ...shedding-reattachment-shedding.•Forecasts using OI and LETKF beat satellite persistence.•LETKF improves forecast skills.
The Local Ensemble Transform Kalman Filter (LETKF) is applied to the parallelized version of the Princeton Ocean Model to estimate the states of Loop Current and eddies in the Gulf of Mexico from April/20 to July/21, 2010 when detailed in situ current measurements were available. Tests are conducted to explore the sensitivity of the LETKF estimates to different parameters, and to systematic additions of different observational datasets which include satellite sea surface height anomaly (SSHA), satellite sea surface temperature (SST), and moored ADCP’s. The results are compared against observations to assess model skills, and also against estimates based on a simpler optimum interpolation (OI) assimilation scheme. With appropriate values of parameters and observational errors, LETKF provides improved estimates of Loop Current and eddy. In particular, the Loop Current in the late spring to summer of 2010 underwent a shedding-reattachment-shedding process. It is shown that such a nonlinear behavior is more accurately captured by LETKF, but not by OI, due to the former’s time-evolving error covariance. Finally, the accuracies of 8-week forecasts initialized from the OI and LETKF analyses and forced by reanalysis winds are compared. This period is particularly challenging to forecast because, instead of a more easily simulated westward propagation at approximately the first-mode baroclinic Rossby wave speed, the newly-shed eddy propagated very slowly, stalled, and finally decayed in the eastern Gulf. Both OI and LETKF beat persistence, but the LETKF significantly improves the eddy’s position and strength throughout the 8-week forecast.
Hepatitis delta virus (HDV) can dramatically worsen liver disease in patients coinfected with hepatitis B virus (HBV). No effective medical therapy exists for HDV. The HDV envelope requires HBV ...surface antigen proteins provided by HBV. Once inside a cell, however, HDV can replicate its genome in the absence of any HBV gene products. In vitro, HDV virion assembly is critically dependent on prenyl lipid modification, or prenylation, of its nucleocapsid-like protein large delta antigen. To overcome limitations of current animal models and to test the hypothesis that pharmacologic prenylation inhibition can prevent the production of HDV virions in vivo, we established a convenient mouse-based model of HDV infection capable of yielding viremia. Such mice were then treated with the prenylation inhibitors FTI-277 and FTI-2153. Both agents were highly effective at clearing HDV viremia. As expected, HDV inhibition exhibited duration-of-treatment dependence. These results provide the first preclinical data supporting the in vivo efficacy of prenylation inhibition as a novel antiviral therapy with potential application to HDV and a wide variety of other viruses.
Hepatitis delta virus (HDV) can dramatically worsen liver disease in patients coinfected with hepatitis B virus (HBV). No effective medical therapy exists for HDV. The HDV envelope requires HBV ...surface antigen proteins provided by HBV. Once inside a cell, however, HDV can replicate its genome in the absence of any HBV gene products. In vitro, HDV virion assembly is critically dependent on prenyl lipid modification, or prenylation, of its nucleocapsid-like protein large delta antigen. To overcome limitations of current animal models and to test the hypothesis that pharmacologic prenylation inhibition can prevent the production of HDV virions in vivo, we established a convenient mouse-based model of HDV infection capable of yielding viremia. Such mice were then treated with the prenylation inhibitors FTI-277 and FTI-2153. Both agents were highly effective at clearing HDV viremia. As expected, HDV inhibition exhibited duration-of-treatment dependence. These results provide the first preclinical data supporting the in vivo efficacy of prenylation inhibition as a novel antiviral therapy with potential application to HDV and a wide variety of other viruses.
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