Effect of an Anterior Cruciate Ligament Rupture on Knee Proprioception Within 2 Years After Conservative and Operative Treatment: A Systematic Review with Meta-Analysis.

BACKGROUND: The anterior cruciate ligament (ACL) plays a major role in knee proprioception and is thus responsible for maintaining knee joint stability and functionality. The available evidence suggests that ACL reconstruction diminishes somatosensory feedback and proprioceptive functioning, which are vital for adequate joint positioning and movement control. OBJECTIVE: The aim of this systematic review and meta-analysis was to investigate the effect of an ACL rupture on knee proprioception after arthroscopic ACL repair surgery or conservative treatment. METHODS: A systematic review with meta-analysis was conducted according to the Preferred Reporting Guidelines for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was performed in the following databases from inception to 10th October 2020: PubMed, Web of Science, SPORTDiscus, Cochrane Library and Scopus. Randomized and non-randomized studies that evaluated proprioception using the joint position sense (JPS) and threshold to detection of passive motion (TTDPM) techniques at 15°-30° knee flexion with an external healthy control group in a time period between 6 and 24 months post injury or operation were included in the analysis. RESULTS: In total, 4857 studies were identified, from which 11 were included in the final quantitative analysis. The results demonstrated that proprioception after arthroscopic ACL repair surgery was significantly lower than in the healthy control group (JPS: standardized mean difference [SMD] 0.57, 95% confidence interval [CI] 0.27-0.87, p < 0.01, n = 6 studies; TTDPM: SMD 0.77, 95% CI 0.20-1.34, p < 0.01, n = 4 studies). There were no significant differences in proprioception between the conservative treatment group and the healthy control group (JPS: SMD 0.57, 95% CI - 0.69 to 1.84, p = 0.37, n = 4 studies; TTDPM: SMD 0.82, 95% CI - 0.02 to 1.65, p = 0.05, n = 2 studies), although measures for TTDPM were close to statistical significance. CONCLUSION: The findings of the present systematic review and meta-analysis revealed that knee proprioception is persistently compromised 6-24 months following surgical treatment of ACL tears compared with healthy controls. The reduced kinesthetic awareness after ACL surgery is of high relevance for optimizing individual treatment plans in these patients. As the current literature is still scarce about the exact underlying mechanisms, further research is needed. TRIAL REGISTRATION: The present systematic review was registered in PROSPERO (CRD42021198617).

Does Knee Arthroscopy for Treatment of Meniscal Damage with Osteoarthritis Delay Knee Replacement Compared to Physical Therapy Alone?

BACKGROUD: To determine patient factors that lead to treatment of meniscal tears with osteoarthritis (OA) with knee arthroscopy (KA) or physical therapy only (PT-only); and to assess differences in clinical outcomes including the time to knee arthroplasty. METHODS: Patients aged ≥ 45 years with OA at meniscal tear diagnosis were followed up from the date of surgery (KA) or first PT visit (PT-only) until partial/total knee replacement surgery, death, disenrollment, or end of study. Demographic and clinical characteristics were compared and used to derive propensity scores. A Cox proportional hazards model was used to estimate the risk of knee replacement surgery and greater healthcare utilization associated with KA vs. PT-only. RESULTS: Among 7,026 patients (KA, 69%; PT-only, 31%), 27% had partial or total knee replacement surgery during follow-up. PT-only patients were older and more likely to be women and had more comorbidities. After accounting for differences between groups, the cumulative incidence of knee replacement was modestly but significantly higher for those who received KA than those who underwent PT-only (hazard ratio, 1.30; 95% confidence interval, 1.17-1.44; p < 0.001), although there was no significant difference in health service utilization, narcotic medication dispenses, or knee injections after initiating treatment. CONCLUSIONS: For patients with meniscal damage complicated by OA, those who underwent KA were 30% more likely to have partial or total knee replacement surgery at any given time than those who had PT alone.

Quantitative Assessment of Regional Mucociliary Clearance in Smokers with Mild-to-Moderate Chronic Obstructive Pulmonary Disease and Chronic Bronchitis from Planar Radionuclide Imaging.

Background: Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study investigates the value of regional clearance measurements in assessing MCC in mild-to-moderate disease. Methods: Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (i) healthy nonsmoking controls (NSCs) (n = 9), (ii) smoking controls (SCs) who were current smokers with normal lung function (n = 10), and (iii) current smokers with mild-to-moderate COPD and bronchitis (n = 15). The mean (±standard deviation) forced expiratory volumes at 1 second (FEV1) for the three groups were 109 (± 18), 94 (± 5), and 78 (± 12), respectively. After inhalation of a technetium-99m labeled aerosol, planar imaging was performed over 4 hours and then at 24 hours. Both lung clearance and tracheobronchial clearance (TBC) (normalized to 24 hours clearance) were calculated for inner and outer lung zones. Inner zone clearance was corrected for input from the outer zone. A novel parameter, the bronchial airways clearance index (BACI), which combined clearance data from both zones, was also evaluated. Regional results were compared with whole lung clearance in the same subjects. Results: Corrected inner zone clearance at 3 hours was not reduced compared with NSC in either SCs or COPD. Outer zone clearance was higher in COPD than in the other groups. Corrected inner zone TBC showed significant reductions in SC and COPD compared with NSC. BACI was significantly reduced in COPD compared with NSC and also correlated with FEV1. The mean BACI for SC was also reduced compared with NSC, but the distribution of results was bimodal, with a significant proportion of subjects having values in the NSC range. Conclusions: Regional MCC demonstrated differences between NSCs, SCs, and subjects with mild-to-moderate COPD, which were not apparent with whole lung measurements.

The Effect of Symptom Duration on Outcomes After Fusion for Degenerative Spondylolisthesis.

STUDY DESIGN: Longitudinal comparative cohort. OBJECTIVES: To determine if the duration of symptoms in patients with degenerative spondylolisthesis affects postoperative outcomes after 1- or 2-level decompression and fusion. METHODS: Patients undergoing primary surgery for grade 1 degenerative spondylolisthesis at a single Quality Outcomes Database (QOD) participating site were identified. Demographic, surgical and patient-reported outcomes (PROs) data, including baseline and 12-month postoperative Oswestry Disability Index (ODI), back pain (BP, 0-10), leg pain (LP, 0-10), and EuroQOL-5D (EQ-5D) scores were collected. Individual medical records were reviewed for data on duration of symptoms prior to surgery. Patients were stratified into 3 cohorts-those with preoperative symptom duration of less than 1 year, 1 to 2 years, or greater than 2 years. RESULTS: Complete data was available in 123 patients. Significant improvement in ODI, BP, and LP scores were observed in all groups. At 12-month follow-up improvement in ODI, BP, or LP was similar among the cohorts; with a trend toward significance with better improvement in LP scores in patients with a symptom duration of less than 1 year to those with symptom duration greater than 2 years (P = .058). CONCLUSIONS: The duration of symptoms up to 2 years prior to surgery may not be a useful predictor of improvement of back pain or disability scores in patients with spondylolisthesis requiring decompression and fusion. Although there was a positive trend for improvement in leg pain for those with a shorter duration of symptoms, this did not reach statistical significance in our study.

Complications after surgical treatment of distal clavicle fractures.

INTRODUCTION: Distal clavicle fractures have low rates of union when treated with conservative measures. Operative treatment is generally recommended for Neer type II and V. Multiple fixation methods exist with no clear gold standard. The goal of the current study is to assess the outcomes and complications of distal clavicle fractures treated with one of three fixation methods: standard clavicular plate, hook plate or suture fixation about the coracoid. METHODS: This is a retrospective cohort study of surgically-treated unstable Neer type II and V distal clavicle fractures in adults. These operations were performed by multiple surgeons within a single healthcare system between January 2010 and September 2012. Patients were divided into three cohorts: pre-contoured clavicular locking plates, hook plates, and suture-only fixation methods. Univariate and mulivariate modeling analyses were performed. RESULTS: A total of 74 distal clavicle fractures comprised the final cohort. Fifty-eight (77%) of these fractures were Neer type II; the remaining 16 (21.6%) were Neer type V. Median follow-up time was 12 months (range 10-28). BMI, smoking status, diabetes, and ASA class were similar among all cohorts. Twenty-one patients were treated with suture fixation alone (28.3%), 37 with a contoured clavicular plate (50%) and 16 with hook plate fixation (21.6%). Twenty-one patients (28.4%) experienced complications, including two hardware failures requiring revision surgery. A total of 10/16 (62.5%) patients with hook plates required hardware removal for irritation, compared to 6/37 (16.2%) with a contoured clavicular plate (OR=8.61, p value=0.001), and none with sutures alone. A total of 3/21 patients (14.2%) treated with suture fixation methods were diagnosed with adhesive capsulitis post-operatively; no patients in the plate fixation groups received this diagnosis. The Neer V group had a higher proportion of any complications (37.5%) compared to Neer II (25.9%), and a higher rate of stiffness (12.5% v. 1.7% in Neer II). CONCLUSION: This study compared the outcomes of three different fixation methods for unstable distal clavicle fractures. The overall union rate with any method of operative intervention was very high (98.6%), consistent with previous studies. Hook plates had a much higher re-operation rate, mostly owing to a higher incidence of hardware removal, an expected outcome owing to the prominence of these plates in the subacromial space. Contoured clavicular plates were associated with a lower incidence of irritation and hardware removal than hook plates, although one patient in this group experienced loss of fracture fixation and went on to asymptomatic radiographic non-union. Suture-only fixation methods had the lowest rate of re-operation, with only one of 21 procedures resulting in failure and requiring revision. However, there was a significantly higher rate of adhesive capsulitis in the suture fixation cohort, perhaps due to the tethering effect of the clavicle to the coracoid or violation of the rotator interval. While this study supports that most distal clavicle fracture fixation methods can achieve stable union, there is a highly variable complication profile associated with each fixation method. The routine use of hook plate fixation cannot be recommended.

Quantitative Assessment of Mucociliary Clearance in Smokers with Mild-to-Moderate Chronic Obstructive Pulmonary Disease and Chronic Bronchitis from Planar Radionuclide Imaging Using the Change in Penetration Index.

Background: Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study compared the use of change in penetration index (PI) with conventional whole lung clearance in assessing MCC in mild-to-moderate disease. Methods: Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (1) healthy nonsmoking controls (n = 9), (2) smoking controls who were current smokers with normal lung function (n = 10), and (3) current smokers with mild-to-moderate COPD and bronchitis (n = 15). The mean (±standard deviation) forced expiratory volume at 1 second (FEV1) for the three groups was 109 (±18), 94 (±5), and 78 (±12), respectively. Following inhalation of a technetium-99m labeled aerosol, planar imaging was performed over 4 hours and then at 24 hours. Total lung clearance and tracheobronchial clearance (TBC; normalized to 24-hour clearance) were calculated. A novel parameter, the normalized change in PI (NOCHIP), was also evaluated. PI is the ratio of counts between outer and inner lung zones normalized to lung volume. Results: More aerosol was deposited in central airways in COPD compared to nonsmoking controls, using 24-hour clearance measurements (p < 0.001). Smoking controls had intermediate values. The optimal endpoint for MCC assessment was chosen to be 3 hours, when intersubject variability was minimal, while preserving a measure of early clearance. There was no statistical difference between the three groups in mean total lung clearance, or TBC, at 3 hours. NOCHIP at 3 hours was reduced significantly, compared to nonsmoking controls, in both smoking controls (p = 0.007) and COPD (p < 0.0001). It also correlated with FEV1 (p = 0.003). A higher proportion of smoking control subjects had NOCHIP values in the nonsmoking control range than in the COPD group. Conclusions: NOCHIP was a more sensitive measure of MCC than whole lung clearance and TBC in mild-to-moderate COPD.

Biomechanical comparison of fixation stability using a Lisfranc plate versus transarticular screws.

BACKGROUND: To obtain adequate fixation in treating Lisfranc soft tissue injuries, the joint is commonly stabilized using multiple transarticular screws; however iatrogenic injury is a concern. Alternatively, two parallel, longitudinally placed plates, can be used to stabilize the 1st and 2nd tarsometatarsal joints; however this may not provide adequate stability along the Lisfranc ligament. Several biomechanical studies have compared earlier methods of fixation using plates to the standard transarticular screw fixation method, highlighting the potential issue of transverse stability using plates. A novel dorsal plate is introduced, intended to provide transverse and longitudinal stability, without injury to the articular cartilage. METHODS: A biomechanical cadaver model was developed to compare the fixation stability of a novel Lisfranc plate to that of traditional fixation, using transarticular screws. Thirteen pairs of cadaveric specimens were tested intact, after a simulated Lisfranc injury, and then following implant fixation, using one method of fixation randomly assigned, on either side of each pair. Optical motion tracking was used to measure the motion between each of the following four bones: 1st metatarsal, 2nd metatarsal, 1st cuneiform, and 2nd cuneiform. Testing included both cyclic abduction loading and cyclic axial loading. RESULTS: Both the Lisfranc plate and screw fixation method provided stability such that the average 3D motions across the Lisfranc joint (between 2nd metatarsal and 1st cuneiform), were between 0.2 and 0.4mm under cyclic abduction loading, and between 0.4 and 0.5mm under cyclic axial loading. Comparing the stability of fixation between the Lisfranc plate and the screws, the differences in motion were all 0.3mm or lower, with no clinically significant differences (p>0.16). CONCLUSIONS: Diastasis at the Lisfranc joint following fixation with a novel plate or transarticular screw fixation were comparable. Therefore, the Lisfranc plate may provide adequate support without risk of iatrogenic injury to the articular cartilage.

Distal fibula fracture fixation: Biomechanical evaluation of three different fixation implants.

BACKGROUND: The goal of this study was to evaluate the biomechanical performance of three distal fibula fracture fixation implants in a matched pair cadaveric fibula model: (1) a 5-hole compression plate with lag screw, (2) a 5-hole locking plate with lag screw, and (3) the 6-hole tabbed-plate with locking screws. METHODS: Three-dimensional motions between the proximal and distal fibular segments were measured under cyclic valgus bending, cyclic compressive axial loading, and cyclic torsional external-rotation loading. During loading, strains were measured on the surfaces of each fibula near the simulated fracture site, and on the plate, to assess load transfer. Bone quality was quantified globally for each donor using bone mineral density (BMD) measured using Dual X-ray absorptiometry (DEXA) and locally at the fracture site using bone mineral content (BMC) measured using peripheral quantitative computed tomography (pQCT). RESULTS: Mean failure loads were below 0.2Nm of valgus bending and below 4Nm of external-rotational torque. Mean failure angulation was below 1degree for valgus bending, and failure rotation was below 7degrees for external-rotation. In the compression plate group, significant correlations were observed between bone quality (global BMD and local BMC) and strain in every one of the five locations (Pearson correlation coefficients >0.95, p<0.05). In contrast, in the locking and tabbed-plate groups, BMD and BMC correlated with far fewer strain locations. CONCLUSIONS: Overall, the tabbed-plate had similar construct stability and strength to the compression and locking plates. However, the distribution of load with the locking and tabbed-plates was not as heavily dependent on bone quality.

Regional assessment of lung function using thin-plate splines to align structural and functional imaging.

Ventilation / perfusion (VQ) Single Photon Emission Computed Tomography (SPECT) imaging provides 3D data of the regional distribution of ventilation and perfusion throughout the lung, but interpretation of the results is difficult without reference to the underlying lung anatomy. Multi-Slice Computed Tomography (MSCT) imaging is able to provide significant anatomical detail in the lung, allowing delineation of regional features such as the lobes. The purpose of this work was to develop software tools to allow the alignment of regions delineated from the MSCT scans, with the corresponding SPECT data, to allow measurements of VQ to be made for anatomically meaningful regions. The technique developed was based on the use of thin-plate splines and the results showed that it was able to provide good alignment between the MSCT and SPECT data.

The human ubiquitin conjugating enzyme UBE2J2 (Ubc6) is a substrate for proteasomal degradation.

The human Ube2J2 enzyme functions in the ubiquitination of proteins at the ER. Here we demonstrate that it, and a second ubiquitin conjugating (Ubc) enzyme Ube2G2, are unstable, and incubation of transfected cells with proteasome inhibitors increased steady-state protein levels. For Ube2J2, pharmacological induction of the unfolded protein response (UPR) did not significantly alter ectopic protein levels, however the effect of proteasomal inhibition was abolished if the enzyme was inactivated or truncated to disrupt its ER-localization. These results suggest for the first time that the steady state expression of Ubcs' may be important in regulating the degradation of ER proteins in mammalian cells.

Airway deposition of nebulized gene delivery nanocomplexes monitored by radioimaging agents.

Receptor-targeted nanocomplexes are nonviral vectors developed for gene delivery to the airway epithelium for the treatment of pulmonary disease associated with cystic fibrosis. The present study aimed to optimize the delivery of the nanocomplex by nebulization, and to monitor the in vivo deposition of radiolabeled vector in the airways of a large animal model by γ-camera scintigraphy. Large White weaner pigs were nebulized with nanocomplexes mixed with technetium-99m radiopharmaceuticals. The aerosol deposition scans suggested that the nebulized radiovectors were deposited mainly in the trachea-main bronchi and in the midregion of the lungs. The plasmid biodistribution, assessed by real-time PCR, correlated with the scintigraphy images. The highest plasmid copy numbers were found in the bronchial areas and in the tissues proximal to the main bronchi bifurcation. Immunohistochemistry detected transgene expression in the tracheal and bronchial ciliated epithelium. Histological analysis of lung tissue showed no evidence of inflammation, and no increase in inflammatory cytokines or inflammatory cells was detected in the bronchoalveolar lavage. The deposition of nebulized nanocomplexes coassociated with technetium-99m can be monitored by nuclear medicine techniques. The use of a noninvasive strategy to follow the delivery of the vector could improve the clinical management of patients undergoing cystic fibrosis gene therapy.

Validation of administrative data sources for endoscopy utilization in colorectal cancer diagnosis.

BACKGROUND: Validation of administrative data is important to assess potential sources of bias in outcome evaluation and to prevent dissemination of misleading or inaccurate information. The purpose of the study was to determine the completeness and accuracy of endoscopy data in several administrative data sources in the year prior to colorectal cancer diagnosis as part of a larger project focused on evaluating the quality of pre-diagnostic care. METHODS: Primary and secondary data sources for endoscopy were collected from the Alberta Cancer Registry, cancer medical charts and three different administrative data sources. 1672 randomly sampled patients diagnosed with invasive colorectal cancer in years 2000-2005 in Alberta, Canada were included. A retrospective validation study of administrative data for endoscopy in the year prior to colorectal cancer diagnosis was conducted. A gold standard dataset was created by combining all the datasets. Number and percent identified, agreement and percent unique to a given data source were calculated and compared across each dataset and to the gold standard with respect to identifying all patients who underwent endoscopy and all endoscopies received by those patients. RESULTS: The combined administrative data and physician billing data identified as high or higher percentage of patients who had one or more endoscopy (84% and 78%, respectively) and total endoscopy procedures (89% and 81%, respectively) than the chart review (78% for both). CONCLUSIONS: Endoscopy data has a high level of completeness and accuracy in physician billing data alone. Combined with hospital in/outpatient data it is more complete than chart review alone.

Tyrosine kinase receptor alteration of renal vasoconstriction in rats is sex- and age-related.

Male rat renal blood vessels undergo reduced contraction to norepinephrine with aging. There is a greater renal vascular impairment in male compared with female rats. We investigated specific tyrosine kinase receptor inhibition of renal interlobar artery responsiveness to phenylephrine in male and female rats at specifically designated ages. Vessels from young male rats contracted much less to phenylephrine when the vessels were pretreated with the tyrosine kinase inhibitors Lavendustin A, HNMPA-(AM)3, or AG1478. Vessels from adult female rats pretreated with Lavendustin A showed no difference in contraction from control, but did demonstrate a slightly reduced contraction when pretreated with AG1478. Middle-aged male rat vessels treated with Lavendustin A demonstrated no inhibition, but the insulin and epidermal growth factor receptor (EGFR) antagonists both induced a decline in contraction. Vessels from aged male rats demonstrated no effect related to the 3 pretreatments. Middle-aged and aged female rats pretreated with any inhibitor demonstrated no inhibitor-dependent alterations. We conclude that maximum contraction of interlobar arteries from adult male rats is reduced when tyrosine kinase receptor activity is reduced. Female rats demonstrated much less inhibitor-related change of contraction.

Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis.

Metazoan internal organs are assembled from polarized tubular epithelia that must set aside an apical membrane domain as a lumenal surface. In a global Caenorhabditis elegans tubulogenesis screen, interference with several distinct fatty-acid-biosynthetic enzymes transformed a contiguous central intestinal lumen into multiple ectopic lumens. We show that multiple-lumen formation is caused by apicobasal polarity conversion, and demonstrate that in situ modulation of lipid biosynthesis is sufficient to reversibly switch apical domain identities on growing membranes of single post-mitotic cells, shifting lumen positions. Follow-on targeted lipid-biosynthesis pathway screens and functional genetic assays were designed to identify a putative single causative lipid species. They demonstrate that fatty-acid biosynthesis affects polarity through sphingolipid synthesis, and reveal ceramide glucosyltransferases (CGTs) as end-point biosynthetic enzymes in this pathway. Our findings identify glycosphingolipids, CGT products and obligate membrane lipids, as critical determinants of in vivo polarity and indicate that they sort new components to the expanding apical membrane.

Uptake and tolerance of adjuvant chemotherapy in early stage NSCLC patients in Alberta, Canada.

Adjuvant chemotherapy for early stage non-small cell lung cancer was approved for provincial insurance coverage in Alberta, Canada in 2004. The purpose of this study was to measure factors related to uptake of chemotherapy in eligible patients and compare toxicity and survival outcomes in the Alberta population with those found in clinical trials. All Alberta residents diagnosed with stage IB-IIB NSCLC from 2004 to 2006 who had surgery and a consultation with an oncologist to discuss initial treatment were included in the study. Diagnostic, demographic, and vital statistics data were obtained from the Alberta Cancer Registry; chart reviews were conducted to identify details related to treatments discussed, refused, co-morbidities, and toxicity. Analyses were conducted to identify factors associated with discussion and receipt of chemotherapy and toxicity. Toxicity and survival were calculated and compared to clinical trial results. 226 patients were included in the study. Adjuvant chemotherapy was not recommended to 57 patients (25%) and 30 patients (13%) refused chemotherapy. Primary reasons for not recommending chemotherapy were co-morbidities and/or frailty (24 patients). Of the 139 patients who began chemotherapy, 47 (34%) stopped treatment early. Stage II patients who received adjuvant chemotherapy had over a 2-fold decrease in risk of death compared to those who did not receive chemotherapy after adjusting for age and co-morbidities. Efforts to improve uptake of adjuvant chemotherapy in patients with stage II NSCLC should be made as the survival advantage appears to be comparable to that found in clinical trials.