Multirater Agreement of the Causes of Anterior Cruciate Ligament Reconstruction Failure

BackgroundAnterior cruciate ligament (ACL) reconstruction failure occurs in up to 10% of cases. Technical errors are considered the most common cause of graft failure despite the absence of validated studies. Limited data are available regarding the agreement among orthopaedic surgeons regarding the causes of primary ACL reconstruction failure and accuracy of graft tunnel placement.HypothesisExperienced knee surgeons have a high level of interobserver reliability in the agreement about the causes of primary ACL reconstruction failure, anatomic graft characteristics, and tunnel placement.Study designCohort study (diagnosis); Level of evidence, 3.MethodsTwenty cases of revision ACL reconstruction were randomly selected from the Multicenter ACL Revision Study (MARS) database. Each case included the patient's history, standardized radiographs, and a concise 30-second arthroscopic video taken at the time of revision demonstrating the graft remnant and location of the tunnel apertures. All 20 cases were reviewed by 10 MARS surgeons not involved with the primary surgery. Each surgeon completed a 2-part questionnaire dealing with each surgeon's training and practice, as well as the placement of the femoral and tibial tunnels, condition of the primary graft, and the surgeon's opinion as to the causes of graft failure. Interrater agreement was determined for each question with the kappa coefficient and the prevalence-adjusted, bias-adjusted kappa (PABAK).ResultsThe 10 reviewers have been in practice an average of 14 years and have performed at least 25 ACL reconstructions per year, and 9 were fellowship trained in sports medicine. There was wide variability in agreement among knee experts as to the specific causes of ACL graft failure. When participants were specifically asked about technical error as the cause for failure, interobserver agreement was only slight (PABAK = 0.26). There was fair overall agreement on ideal femoral tunnel placement (PABAK = 0.55) but only slight agreement on whether a femoral tunnel was too anterior (PABAK = 0.24) and fair agreement on whether it was too vertical (PABAK = 0.46). There was poor overall agreement for ideal tibial tunnel placement (PABAK = 0.17).ConclusionThis study suggests that more objective criteria are needed to accurately determine the causes of primary ACL graft failure as well as the ideal femoral and tibial tunnel placement in patients undergoing revision ACL reconstruction

Subsequent Surgery After Revision Anterior Cruciate Ligament Reconstruction: Rates and Risk Factors From a Multicenter Cohort

BackgroundWhile revision anterior cruciate ligament reconstruction (ACLR) can be performed to restore knee stability and improve patient activity levels, outcomes after this surgery are reported to be inferior to those after primary ACLR. Further reoperations after revision ACLR can have an even more profound effect on patient satisfaction and outcomes. However, there is a current lack of information regarding the rate and risk factors for subsequent surgery after revision ACLR.PurposeTo report the rate of reoperations, procedures performed, and risk factors for a reoperation 2 years after revision ACLR.Study designCase-control study; Level of evidence, 3.MethodsA total of 1205 patients who underwent revision ACLR were enrolled in the Multicenter ACL Revision Study (MARS) between 2006 and 2011, composing the prospective cohort. Two-year questionnaire follow-up was obtained for 989 patients (82%), while telephone follow-up was obtained for 1112 patients (92%). If a patient reported having undergone subsequent surgery, operative reports detailing the subsequent procedure(s) were obtained and categorized. Multivariate regression analysis was performed to determine independent risk factors for a reoperation.ResultsOf the 1112 patients included in the analysis, 122 patients (11%) underwent a total of 172 subsequent procedures on the ipsilateral knee at 2-year follow-up. Of the reoperations, 27% were meniscal procedures (69% meniscectomy, 26% repair), 19% were subsequent revision ACLR, 17% were cartilage procedures (61% chondroplasty, 17% microfracture, 13% mosaicplasty), 11% were hardware removal, and 9% were procedures for arthrofibrosis. Multivariate analysis revealed that patients aged <20 years had twice the odds of patients aged 20 to 29 years to undergo a reoperation. The use of an allograft at the time of revision ACLR (odds ratio [OR], 1.79; P = .007) was a significant predictor for reoperations at 2 years, while staged revision (bone grafting of tunnels before revision ACLR) (OR, 1.93; P = .052) did not reach significance. Patients with grade 4 cartilage damage seen during revision ACLR were 78% less likely to undergo subsequent operations within 2 years. Sex, body mass index, smoking history, Marx activity score, technique for femoral tunnel placement, and meniscal tearing or meniscal treatment at the time of revision ACLR showed no significant effect on the reoperation rate.ConclusionThere was a significant reoperation rate after revision ACLR at 2 years (11%), with meniscal procedures most commonly involved. Independent risk factors for subsequent surgery on the ipsilateral knee included age <20 years and the use of allograft tissue at the time of revision ACLR

Phytochemical composition and bio-functional properties of Apis mellifera propolis from Kenya

There is an increased demand for natural products like propolis, yet little information is available about the chemical composition of African propolis and its bio-functional properties. Therefore, in this study, we aimed to quantify the phytochemicals and determine the antioxidant and antimicrobial properties of Apis mellifera propolis (n = 59) sourced from various regions in Kenya. Principal component analysis (PCA) showed that the sampling region had a remarkable impact on the propolis's composition and bio-functional properties. Generally, the propolis contained high amounts of phytochemicals, particularly alkaloids (5.76 g CE/100 g) and phenols (2.24 g GAE/100 g). Furthermore, analysis of propolis by gas chromatography–mass spectrometry (GC-MS) revealed various compounds with varying bio-functional activities. These compounds included triterpenoids alpha- and beta-amyrin, oleanen-3-yl-acetate, urs-12-en-24-oic acid, lanosta-8,24-dien-3-one, and hydrocarbons tricosane and nondecane, which have been reported to have either antimicrobial or antioxidant activities. The propolis samples collected from hotter climatic conditions contained a higher composition of phytochemicals, and additionally, they displayed higher antioxidant and antimicrobial activities than those obtained from cooler climatic conditions. Key findings of this study demonstrate the occurrence of relatively high phytochemical content in Kenya's propolis, which has antioxidant and antimicrobial properties; hence this potential could be harnessed for disease control

In vitro and in vivo effects of 2,4 diaminoquinazoline inhibitors of the decapping scavenger enzyme DcpS: Context-specific modulation of SMN transcript levels

<div><p>C5-substituted 2,4-diaminoquinazoline inhibitors of the decapping scavenger enzyme DcpS (DAQ-DcpSi) have been developed for the treatment of spinal muscular atrophy (SMA), which is caused by genetic deficiency in the Survival Motor Neuron (SMN) protein. These compounds are claimed to act as <i>SMN2</i> transcriptional activators but data underlying that claim are equivocal. In addition it is unclear whether the claimed effects on <i>SMN2</i> are a direct consequence of DcpS inhibitor or might be a consequence of lysosomotropism, which is known to be neuroprotective. DAQ-DcpSi effects were characterized in cells <i>in vitro</i> utilizing DcpS knockdown and 7-methyl analogues as probes for DcpS vs non-DcpS-mediated effects. We also performed analysis of <i>Smn</i> transcript levels, RNA-Seq analysis of the transcriptome and SMN protein in order to identify affected pathways underlying the therapeutic effect, and studied lysosomotropic and non-lysosomotropic DAQ-DCpSi effects in 2B/- SMA mice. Treatment of cells caused modest and transient <i>SMN2</i> mRNA increases with either no change or a decrease in <i>SMNΔ7</i> and no change in <i>SMN1</i> transcripts or SMN protein. RNA-Seq analysis of DAQ-DcpSi-treated N2a cells revealed significant changes in expression (both up and down) of approximately 2,000 genes across a broad range of pathways. Treatment of 2B/- SMA mice with both lysomotropic and non-lysosomotropic DAQ-DcpSi compounds had similar effects on disease phenotype indicating that the therapeutic mechanism of action is not a consequence of lysosomotropism. In striking contrast to the findings <i>in vitro</i>, <i>Smn</i> transcripts were robustly changed in tissues but there was no increase in SMN protein levels in spinal cord. We conclude that DAQ-DcpSi have reproducible benefit in SMA mice and a broad spectrum of biological effects <i>in vitro</i> and <i>in vivo</i>, but these are complex, context specific, and not the result of simple <i>SMN2</i> transcriptional activation.</p></div

Effect of DAQ-DcpSi treatment on <i>Smn</i> transcript levels in tissues from 2B/- SMA mice and healthy 2B/+ littermate controls.

<p>Animals were dosed with either vehicle, RG3039 (6 mg/kg) or PF-06738066 (10 mg/kg) BID via intraperitoneal injection from P4-P16 and were sacrificed 12 hours following the last dose for collection of tissues. RNA was prepared and analyzed using ddPCR as described in materials and methods. All gene expression was normalized to <i>PSMD14</i> expression and expressed relative to that in vehicle-treated 2B/- mice. All data shown as mean ± s.e.m. Numbers of animals in each data set were: 2B/- Vehicle (22); 2B/- RG3039(9); 2B/- PF-06738066 (13); 2B/+ Vehicle (7); 2B/+ RG3039(9); 2B/+ PF-06738066 (10). Significance using Student’s <i>t</i>-test: <i>P</i><0.05 (*), <i>P</i><0.01(**), <i>P</i><0.001(***), <i>P</i><0.0001(****).</p

Effect of active DAQ-DcpSi and their 7-methyl analogues on <i>PAQR8</i> and <i>DPM3</i> transcripts.

<p>SMA-derived lymphoblasts were treated with active DAQ-DcpSi (RG3039, PF-06738066) or their 7-methyl analogues (PF-06802336 and PF-06832344 respectively) and the levels of <i>PAQR8</i> and <i>DPM3</i> transcripts measured using ddPCR. All data shown as mean ± s.e.m. and where not shown error bars are within the size of the symbols. Significant P-values were denoted as <i>P</i><0.05 (*), <i>P</i><0.01(**), <i>P</i><0.001(***), <i>P</i><0.0001(****).</p