Quadriceps tendon autograft is becoming increasingly popular in revision ACL reconstruction

© 2021, The Author(s). Purpose: To evaluate trends in revision anterior cruciate ligament reconstruction (ACL-R), with emphasis on intra-articular findings, grafts, and concurrent procedures. It was hypothesized that revision ACL-Rs over time show a trend toward increased complexity with increased use of autografts over allografts. Methods: This was a two-center retrospective study including patients undergoing revision ACL-R between 2010 and 2020. Demographic and surgical data including intra-articular findings and concurrent procedures were collected and compared for the time periods 2010–2014 and 2015–2020. All collected variables were compared between three pre-defined age groups (\u3c 20 years, 20–30 years, \u3e 30 years), right and left knees, and males and females. A time series analysis was performed to assess trends in revision ACL-R. Results: This study included 260 patients with a mean age of 26.2 ± 9.4 years at the time of the most recent revision ACL-R, representing the first, second, third, and fourth revision ACL-R for 214 (82%), 35 (14%), 10 (4%), and 1 (\u3c 1%) patients, respectively. Patients age \u3e 30 years showed a significantly longer mean time from primary ACL-R to most recent revision ACL-R (11.1 years), compared to patients age \u3c 20 years (2.2 years, p \u3c 0.001) and age 20–30 years (5.5 years, p \u3c 0.05). Quadriceps tendon autograft was used significantly more often in 2015–2020 compared to 2010–2014 (49% vs. 18%, p \u3c 0.001). A high rate of concurrently performed procedures including meniscal repairs (45%), lateral extra-articular tenodesis (LET; 31%), osteotomies (13%), and meniscal allograft transplantations (11%) was shown. Concurrent LET was associated with intact cartilage and severely abnormal preoperative knee laxity and showed a statistically significant and linear increase over time (p \u3c 0.05). Intact cartilage (41%, p \u3c 0.05), concurrent medial meniscal repairs (39%, p \u3c 0.05), and LET (35%, non-significant) were most frequently observed in patients aged \u3c 20 years. Conclusion: Quadriceps tendon autograft and concurrent LET are becoming increasingly popular in revision ACL-R. Intact cartilage and severely abnormal preoperative knee laxity represent indications for LET in revision ACL-R. The high rate of concurrent procedures observed demonstrates the high surgical demands of revision ACL-R. Level of evidence: Level III

Meniscal allograft transplantation in the Netherlands: long-term survival, patient-reported outcomes, and their association with preoperative complaints and interventions

Purpose Evaluation of survival of meniscal allograft transplantation (MAT) and postoperative patient-reported outcome (PRO), and their association with prior interventions of the knee. Methods A prospective consecutive study of 109 consecutive patients who had an arthroscopic meniscal allograft transplantation (MAT) between 1999 and 2017 by a single surgeon. Patients were assessed with KOOS scores, preoperative and after a minimal follow-up of 2 years. Furthermore, two anchor questions (whether expectations were met and overall satisfaction, on a five-point Likert scale) were asked. Additionally, prior interventions to MAT were evaluated. Results Prior to MAT, patients had undergone an average of 2.8 (range 1-14) of surgical procedures of the knee. Overall, mean allograft survival was 16.1 years (95% CI 14.8-17.5 years). Higher age at surgery was associated with lower MAT survival: hazard ratio for MAT failure was 1.19 per year increase (95% CI 1.04 to 1.36,p = 0.009). At 4.5 years (IQR, 2-9) of follow-up, all KOOS score were still improved compared to baseline. Age below 35 years, simultaneous anterior cruciate ligament reconstruction and number of knee surgeries before MAT were associated with lower KOOS scores. Overall patient expectations and overall satisfaction after MAT were not associated with preoperative patient characteristics nor with the number or kind of preoperative interventions. Conclusion Meniscal allograft transplantation has a good overall survival with a clinically relevant improvement. Both meniscal allograft survival and PRO were associated with age. PRO was lower in patients younger than 35 years at time of MAT and meniscal allograft survival was worse in patients older than 50 years. PRO was associated with preoperative patient characteristics and number of surgical procedures prior to MAT. All patients reported improved postoperative satisfaction and met expectations after MAT, both independent of the preoperative history of knee interventions.Orthopaedics, Trauma Surgery and Rehabilitatio

Schwinger boson theory of anisotropic ferromagnetic ultrathin films

Ferromagnetic thin films with magnetic single-ion anisotropies are studied within the framework of Schwinger bosonization of a quantum Heisenberg model. Two alternative bosonizations are discussed. We show that qualitatively correct results are obtained even at the mean-field level of the theory, similar to Schwinger boson results for other magnetic systems. In particular, the Mermin-Wagner theorem is satisfied: a spontaneous magnetization at finite temperatures is not found if the ground state of the anisotropic system exhibits a continuous degeneracy. We calculate the magnetization and effective anisotropies as functions of exchange interaction, magnetic anisotropies, external magnetic field, and temperature for arbitrary values of the spin quantum number. Magnetic reorientation transitions and effective anisotropies are discussed. The results obtained by Schwinger boson mean-field theory are compared with the many-body Green's function technique.Comment: 14 pages, including 7 EPS figures, minor changes, final version as publishe

Association of germline variation with the survival of women with BRCA1/2 pathogenic variants and breast cancer

Germline genetic variation has been suggested to influence the survival of breast cancer patients independently of tumor pathology. We have studied survival associations of genetic variants in two etiologically unique groups of breast cancer patients, the carriers of germline pathogenic variants in BRCA1 or BRCA2 genes. We found that rs57025206 was significantly associated with the overall survival, predicting higher mortality of BRCA1 carrier patients with estrogen receptor-negative breast cancer, with a hazard ratio 4.37 (95% confidence interval 3.03-6.30, P = 3.1 × 10-9). Multivariable analysis adjusted for tumor characteristics suggested that rs57025206 was an independent survival marker. In addition, our exploratory analyses suggest that the associations between genetic variants and breast cancer patient survival may depend on tumor biological subgroup and clinical patient characteristics

Identification of independent association signals and putative functional variants for breast cancer risk through fine-scale mapping of the 12p11 locus.

BACKGROUND: Multiple recent genome-wide association studies (GWAS) have identified a single nucleotide polymorphism (SNP), rs10771399, at 12p11 that is associated with breast cancer risk. METHOD: We performed a fine-scale mapping study of a 700 kb region including 441 genotyped and more than 1300 imputed genetic variants in 48,155 cases and 43,612 controls of European descent, 6269 cases and 6624 controls of East Asian descent and 1116 cases and 932 controls of African descent in the Breast Cancer Association Consortium (BCAC; http://bcac.ccge.medschl.cam.ac.uk/ ), and in 15,252 BRCA1 mutation carriers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Stepwise regression analyses were performed to identify independent association signals. Data from the Encyclopedia of DNA Elements project (ENCODE) and the Cancer Genome Atlas (TCGA) were used for functional annotation. RESULTS: Analysis of data from European descendants found evidence for four independent association signals at 12p11, represented by rs7297051 (odds ratio (OR) = 1.09, 95 % confidence interval (CI) = 1.06-1.12; P = 3 × 10(-9)), rs805510 (OR = 1.08, 95 % CI = 1.04-1.12, P = 2 × 10(-5)), and rs1871152 (OR = 1.04, 95 % CI = 1.02-1.06; P = 2 × 10(-4)) identified in the general populations, and rs113824616 (P = 7 × 10(-5)) identified in the meta-analysis of BCAC ER-negative cases and BRCA1 mutation carriers. SNPs rs7297051, rs805510 and rs113824616 were also associated with breast cancer risk at P < 0.05 in East Asians, but none of the associations were statistically significant in African descendants. Multiple candidate functional variants are located in putative enhancer sequences. Chromatin interaction data suggested that PTHLH was the likely target gene of these enhancers. Of the six variants with the strongest evidence of potential functionality, rs11049453 was statistically significantly associated with the expression of PTHLH and its nearby gene CCDC91 at P < 0.05. CONCLUSION: This study identified four independent association signals at 12p11 and revealed potentially functional variants, providing additional insights into the underlying biological mechanism(s) for the association observed between variants at 12p11 and breast cancer risk.UK funding includes Cancer Research UK and NIH.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13058-016-0718-

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat