Xueliang Pan

Autologous Chondrocyte Implantation: A Systematic Review

BACKGROUNDnThe purpose of the present study was to determine (1) whether the current literature supports the choice of using autologous chondrocyte implantation over other cartilage procedures with regard to clinical outcome, magnetic resonance imaging, arthroscopic assessment, and durability of treatment, (2) whether the current literature supports the use of a specific generation of autologous chondrocyte implantation, and (3) whether there are patient-specific and defect-specific factors that influence outcomes after autologous chondrocyte implantation in comparison with other cartilage repair or restoration procedures.nnnMETHODSnWe conducted a systematic review of multiple databases in which we evaluated Level-I and II studies comparing autologous chondrocyte implantation with another cartilage repair or restoration technique as well as comparative intergenerational studies of autologous chondrocyte implantation. The methodological quality of studies was evaluated with use of Delphi list and modified Coleman methodology scores. Effect size analysis was performed for all outcome measures.nnnRESULTSnThirteen studies (917 subjects) were included. Study methodological quality improved with later publication dates. The mean modified Coleman methodology score was 54 (of 100). Patients underwent autologous chondrocyte implantation (n = 604), microfracture (n = 271), or osteochondral autograft (n = 42). All surgical techniques demonstrated improvement in comparison with the preoperative status. Three of seven studies showed better clinical outcomes after autologous chondrocyte implantation in comparison with microfracture after one to three years of follow-up, whereas one study showed better outcomes two years after microfracture and three other studies showed no difference in these treatments after one to five years. Clinical outcomes after microfracture deteriorated after eighteen to twenty-four months (in three of seven studies). Autologous chondrocyte implantation and osteochondral autograft demonstrated equivalent short-term clinical outcomes, although there was more rapid improvement after osteochondral autograft (two studies). Although outcomes were equivalent between first and second-generation autologous chondrocyte implantation and between open and arthroscopic autologous chondrocyte implantation, complication rates were higher with open, periosteal-cover, first-generation autologous chondrocyte implantation (four studies). Younger patients with a shorter preoperative duration of symptoms and fewer prior surgical procedures had the best outcomes after both autologous chondrocyte implantation and microfracture. A defect size of >4 cm(2) was the only factor predictive of better outcomes when autologous chondrocyte implantation was compared with a non-autologous chondrocyte implantation surgical technique.nnnCONCLUSIONSnCartilage repair or restoration in the knee provides short-term success with microfracture, autologous chondrocyte implantation, or osteochondral autograft. There are patient-specific and defect-specific factors that influence clinical outcomes.

Efficacy of Surgery for Femoroacetabular Impingement A Systematic Review

Background Recent case studies on the surgical treatment of femoroacetabular impingement (FAI) have introduced a large amount of clinical data. However, there has been no clear consensus on its efficacy. Hypothesis The current literature can be clarified to address 4 questions: (1) Does treatment for FAI succeed in improving symptoms? (2) In which subset of patients should treatment for FAI be avoided? (3) Is labral refixation superior to simple resection? (4) Does treatment for FAI alter the natural progression of osteoarthritis in this group of typically young patients? Study Design Systematic review. Methods Twenty-three reports of case studies on the surgical treatment of FAI were identified and a systematic review was conducted. Data from each study were collected to answer each of the 4 focus questions. Results This review of 970 cases included 1 level II evidence trial, 2 level III studies, and 20 level IV studies. Based on patient outcome scores and effect size, all studies demonstrated improvement of patient symptoms. Up to 30% of patients will eventually require total hip arthroplasty; those patients with Outerbridge grade III or IV cartilage damage seen intraoperatively or with preoperative radiographs showing greater than Tonnis grade I osteoarthritis will have worse outcomes with treatment for FAI. Only 2 studies directly compared labral refixation with labral debridement. Several studies reported postoperative osteoarthritis findings; only a minority of these patients had progression of their osteoarthritis. Conclusion Surgical treatment for FAI reliably improves patient symptoms in the majority of patients without advanced osteoarthritis or chondral damage. Early evidence supports labral refixation. It is too soon to predict whether progression of osteoarthritis is delayed. Clinical Relevance These results may be used to help predict the outcome of surgical treatment of FAI in different patient populations and to assess the need for labral refixation.

Knee moments during run-to-cut maneuvers are associated with lateral trunk positioning

Non-contact anterior cruciate ligament (ACL) injuries account for approximately 70% of ACL ruptures and often occur during a sudden change in direction or pivot. Decreased neuromuscular control of the trunk in a controlled perturbation task has previously been associated with ACL injury incidence, while knee abduction moments and tibial internal rotation moments have been associated with ACL strain and ACL injury incidence. In this study, the association between movement of the trunk during a run-to-cut maneuver and loading of the knee during the same activity was investigated. External knee moments and trunk angles were quantified during a run-to-cut maneuver for 29 individuals. The trunk angles examined were outside tilt (frontal plane angle of the torso from vertical), angle between the ground reaction force (GRF) and the torso in the plane containing the GRF and shoulders (torso-GRF_shoulders); and angle between GRF and torso in the plane containing the GRF and pelvis (torso-GRF_pelvis). Significant positive associations were found between torso angles and peak knee abduction moments (outside tilt, p=0.002; and torso-GRF_shoulders, p=0.036) while a significant negative association was found between peak tibial internal rotation moment and outside tilt (p=0.021). Because the peaks of these moments occur at different times and minimal axial rotation moment is observed at peak knee abduction moment (-0.29±0.46%BW*ht), the positive association between peak knee abduction moment and torso lean suggests that increasing torso lean may increase ACL load and risk of injury.

Heterogeneous atypical cell populations are present in blood of metastatic breast cancer patients

IntroductionCirculating tumor cells (CTCs) are commonly isolated from the blood by targeting the epithelial cell adhesion molecule (EpCAM) through positive selection. However, EpCAM can be downregulated during metastatic progression, or it can be initially not present. We designed the present prospective trial to characterize CTCs as well as other circulating cell populations in blood samples from women with metastatic breast cancer without EpCAM-dependent enrichment and/or isolation technology.MethodsA total of 32 patients with metastatic breast cancer were enrolled, and blood samples were processed using a previously described negative depletion immunomagnetic methodology. Samples from healthy volunteers were run as controls (nu2009=u20095). Multistep sequential labeling was performed to label and fix cell-surface markers followed by permeabilization for cytokeratins (CK) 8, 18 and 19. Multiparametric flow cytometry (FCM) analysis was conducted using a BD LSR II flow cytometer or a BD FACSAria II or FACSAria III cell sorter. Immunocytochemical staining on postenrichment specimens for DAPI, EpCAM, CD45, CK, epidermal growth factor receptor and vimentin was performed. Expression of these markers was visualized using confocal microscopy (CM).ResultsCD45-negative/CK-positive (CD45− CK+) populations with EpCAMu2009+u2009and EpCAMu2009−u2009expression were identified with both FCM and CM from the negatively enriched patient samples. In addition, EpCAMu2009+u2009and EpCAMu2009−u2009populations that were CKu2009+u2009and coexpressing the pan-hematopoietic marker CD45 were also noted. There were more CKu2009+u2009EpCAMu2009−u2009events/ml than CKu2009+u2009EpCAMu2009+u2009events/ml in both the CD45− and CD45+ fractions (both statistically significant at Pu2009≤u20090.0005). The number of CKu2009+u2009CD45− and CKu2009+u2009CD45+ events per milliliter in blood samples (regardless of EpCAM status) was higher in patient samples than in normal control samples (Pu2009≤u20090.0005 and Pu2009≤u20090.026, respectively). Further, a significant fraction of the CKu2009+u2009CD45+ events also expressed CD68, a marker associated with tumor-associated macrophages. Higher levels of CD45-CKu2009+u2009EpCAMu2009−u2009were associated with worse overall survival (Pu2009=u20090.0292).ConclusionsMetastatic breast cancer patients have atypical cells that are CKu2009+u2009EpCAMu2009−u2009circulating in their blood. Because a substantial number of these patients do not have EpCAMu2009+u2009CTCs, additional studies are needed to evaluate the role of EpCAMu2009−u2009circulating cells as a prognostic and predictive marker.

Lumbopelvic Control and Days Missed Because of Injury in Professional Baseball Pitchers

Background: Recently, lumbopelvic control has been linked to pitching performance, kinematics, and loading; however, poor lumbopelvic control has not been prospectively investigated as a risk factor for injuries in baseball pitchers. Hypothesis: Pitchers with poor lumbopelvic control during spring training are more likely to miss ≥30 days because of an injury through an entire baseball season than pitchers with good lumbopelvic control. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 347 professional baseball pitchers were enrolled into the study during the last 2 weeks of spring training and stayed with the same team for the entire season. Lumbopelvic control was quantified by peak anterior-posterior deviation of the pelvis relative to the starting position during a single-leg raise test (APScore). Days missed because of an injury through the entire season were recorded by each team’s medical staff. Results: A higher APScore was significantly associated with a higher likelihood of missing ≥30 days (P = .023, χ2 test). When divided into tertiles based on their APScore, participants in the highest tertile were 3.0 times and 2.2 times more likely to miss at least 30 days throughout the course of a baseball season relative to those in the lowest or middle tertiles, respectively. A higher APScore was also significantly associated with missing more days because of an injury within participants who missed at least 1 day (P = .018, ANOVA), with participants in the highest tertile missing significantly more days (mean, 98.6 days) than those in the middle tertile (mean, 45.8 days; P = .017) or lowest tertile (mean, 43.8 days; P = .017). Conclusion: This study found that poor lumbopelvic control in professional pitchers was associated with an increased risk of missing significant time because of an injury.

Evidence for joint moment asymmetry in healthy populations during gait

The purpose of this study was to determine the presence and prevalence of asymmetry in lower extremity joint moments within and across healthy populations during overground walking. Bilateral gait data from several studies performed at two institutions were pooled from 182 healthy, pain-free subjects. Four distinct populations were identified based on age, activity level and body mass index. Mean peak external joint moments were calculated from three to six trials of level overground walking at self-selected speed for each subject. Right and left limb moments were reclassified as greater or lesser moment for each subject to prevent obscuring absolute asymmetry due to averaging over positive and negative asymmetries across subjects. A clinically relevant asymmetry measure was calculated from the peak joint moments with an initial chosen cutoff value of 10%. Confidence intervals for the proportion of subjects with greater than 10% asymmetry between limbs were estimated based on the binomial distribution. We found a high amount of asymmetry between the limbs in healthy populations. More than half of our overall population exceeded 10% asymmetry in peak hip and knee flexion and adduction moments. Group medians exceeded 10% asymmetry for all variables in all populations. This may have important implications on gait evaluations, particularly clinical evaluations or research studies where asymmetry is used as an outcome. Additional research is necessary to determine acceptable levels of joint moment asymmetry during gait and to determine whether asymmetrical joint moments influence the development of symptomatic pathology or success of lower extremity rehabilitation.

Sex Differences in Self-Reported Hip Function Up to 2 Years After Arthroscopic Surgery for Femoroacetabular Impingement

Background: Femoroacetabular impingement (FAI) is a significant cause of disability in young adults. Hip arthroscopic surgery restores bony congruence and improves function in the majority of patients, but recent evidence indicates that women may experience worse pre- and postoperative function than men. Purpose/Hypothesis: The purpose of this study was to identify whether self-reported hip function differed between men and women with symptomatic FAI. The hypothesis was that mean self-reported hip function scores would improve after arthroscopic surgery but that women would report poorer function than men both before and up to 2 years after arthroscopic surgery. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 229 patients (68.4% women; mean [±SD] age, 31.6 ± 10.8 years; mean [±SD] body mass index, 26.8 ± 11.9 kg/m2) underwent hip arthroscopic surgery for unilateral symptomatic FAI. All eligible and consenting patients with radiologically and clinically confirmed FAI completed the International Hip Outcome Tool (iHOT-33) and the Hip Outcome Score activities of daily living subscale (HOS-ADL) before hip arthroscopic surgery and at 3, 6, 12, and 24 months after arthroscopic surgery. A linear mixed model for repeated measures was used to test for differences in self-reported hip function between men and women over the study period (P ≤ .05). Results: There were no significant time × sex interactions for either the HOS-ADL (P = .12) or iHOT-33 (P = .64), but both measures showed significant improvements between the preoperative time point and each of the 4 follow-up points (P < .0001); however, self-reported hip function did not improve between 6 and 24 months after arthroscopic surgery (P ≥ .11). Post hoc independent t tests indicated that women reported poorer hip function than did men before surgery (P ≤ .003) both on the HOS-ADL (mean ± standard error of the mean [SEM], 67.4 ± 1.9 [men] vs 60.5 ± 1.3 [women]) and iHOT-33 (mean ± SEM, 38.0 ± 1.9 [men] vs 30.9 ± 1.3 [women]); scores were not different between sexes at any other time point. Conclusion: These findings indicate improvements in self-reported hip function in patients with FAI, regardless of sex, until 6 months after hip arthroscopic surgery. Although women reported poorer preoperative function than did men, the differences were not significant 2 years after surgery.

Hip adductor activations during run-to-cut manoeuvres in compression shorts: implications for return to sport after groin injury

Abstract Athletes at high risk of groin strains in sports such as hockey and soccer often choose to wear shorts with directional compression to aid in prevention of or recovery from hip adductor strains. Large, eccentric contractions are known to result in or exacerbate strain injuries, but it is unknown if these shorts have a beneficial effect on hip adductor muscle activity. In this study, surface electromyography (EMG) of the adductor longus and ground reaction force (GRF) data were obtained simultaneously on 29 healthy individuals without previous history of serious injury while performing unanticipated 45° run-to-cut manoeuvres in a laboratory setting wearing shorts with non-directional compression (control, HeatGear, Under Armour, USA) or shorts with directional compression (directional, CoreShort PRO, Under Armour, USA), in random order. Average adductor activity in the stance leg was significantly lower in the directional condition than in the control condition during all parts of stance phase (all P < 0.042). From this preliminary analysis, wearing directional compression shorts appears to be associated with reduced stance limb hip adductor activity. Athletes seeking to reduce demand on the hip adductors as they approach full return to activities may benefit from the use of directional compression shorts.

Risk factors for anthracycline-associated cardiotoxicity

PurposeCarbonyl reductase (CBR) catalyzes anthracycline metabolism, and single nucleotide polymorphisms (SNPs) in CBR impact metabolic efficiency. In pediatric patients, homozygosity for the major allele (G) in the CBR3 gene was associated with increased risk of anthracycline cardiotoxicity. We hypothesized that CBR SNPs contribute to cardiotoxicity in adults.MethodsWe retrospectively identified female breast cancer patients in the Columbus Breast Tissue Bank Registry treated with adriamycin and cytoxan (AC) from 2003 to 2012. We selected patients who developed cardiomyopathy, defined as a drop in ejection fraction to <50xa0% or >15xa0% decrease from pre-therapy. Univariate and multivariate logistic regressions were performed to identify cardiotoxicity risk factors. SNPs were genotyped, and frequency of the major allele (G)/minor allele (A) of the CBR3 and CBR1 genes was calculated.ResultsWe identified 52 cases of cardiotoxicity after AC and 110 controls. Multivariate analysis showed that trastuzumab (pu2009=u20090.009), diabetes (pu2009=u20090.05), and consumption of >8 alcoholic drinks/week (pu2009=u20090.024) were associated with higher cardiotoxicity risk. Moderate alcohol consumption (<8 drinks/week) was associated with lower risk (pu2009=u20090.009). No association was identified between CBR SNPs and cardiotoxicity (CBR1 pu2009=u20090.261; CBR3 pu2009=u20090.556).ConclusionsThis is the first study to evaluate SNPs in the CBR pathway as predictors of AC cardiotoxicity in adults. We did not observe any significant correlation between cardiotoxicity and SNPs within the CBR pathway. Further investigation into CBR SNPs in a larger adult sample is needed. Additional exploration into genomic predictors of anthracycline cardiotoxicity may allow for the development of preventative and therapeutic strategies for those at risk.

Treatment of Avascular Necrosis of the Femoral Head Utilising Free Vascularised Fibular Graft: A Systematic Review:

We conducted a systematic review to determine whether the literature supports the use of free vascularised fibular graft (FVFG) over other salvage procedures for the treatment of avascular necrosis (AVN) of the femoral head, and if there are patient-specific and defect-specific factors that may predict better outcomes after FVFG. Fifteen total studies were identified for inclusion. Three comparative studies showed an overall statistically significant superiority of FVFG over NVFG; two comparative studies demonstrated FVFG better than core decompression. One study show a better but not statistically significant superiority of FVFG comparing with vascularised iliac pedicle bone graft procedures, likely due to small sample size. This review suggests that vascularised fibular grafting is a better treatment option than core decompression and nonvascularised fibular grafting.