Lower anxiety level to perform movements after revision anterior cruciate ligament reconstruction with lateral extra-articular tenodesis compared to without lateral extra-articular tenodesis.

PURPOSE: To evaluate the anxiety level to perform movements in patients after revision anterior cruciate ligament reconstruction (ACLR) combined with lateral extra-articular tenodesis (LET) compared to patients after revision ACLR without LET. METHODS: Ninety patients who underwent revision ACLR with ipsilateral bone-patellar tendon-bone autograft and with a minimum of 12 months follow-up were included in this study. Patients were divided into two groups: patients who received revision ACLR in combination with LET (revision ACLR_LET group; mean follow-up: 29.4 months, range: 12-80 months), and patients who received revision ACLR without LET (revision ACLR group; mean follow-up: 61.1 months, range: 22-192 months). All patients filled in a questionnaire about anxiety level related to physical activity and sports, the Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee subjective form (IKDCsubjective), and the Tegner Activity Score. RESULTS: Patients in the revision ACLR_LET group had a significantly lower anxiety level to perform movements than patients in the revision ACLR group (p < 0.05). No significant differences were found in KOOS, IKDCsubjective, and Tegner Activity Scores. CONCLUSIONS: Patients who received LET in addition to revision ACLR have a lower anxiety level to perform movements than patients with revision ACLR alone, despite non-different subjective functional outcomes. STUDY DESIGN: Retrospective cohort study, Level of evidence: III.

12-Year clinical and radiological results of a double-blind randomized controlled trial comparing posterior cruciate-retaining versus posterior-stabilized total knee arthroplasty.

BACKGROUND: A subject of ongoing debate among orthopedic surgeons is the importance of preserving the posterior cruciate ligament in total knee arthroplasty (TKA), but long-term survival studies are scarce. The aim of this study was to compare long-term survival rates, and clinical and radiological follow up of a double-blind randomized controlled trial comparing posterior cruciate-retaining (PCR) versus posterior-stabilizing (PS) implant design of an AGC TKA. METHODS: A total of 114 patients were included in the survival analysis (PCR n = 61; PS n = 53). Forty-five patients (PCR n = 25; PS n = 20) participated in the long-term follow up using patient-reported outcome measures (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Short-Form Health Survey (SF-36) and Kujala score (measuring anterior knee pain)). Thirty-one patients were assessed with a physical test (Knee Society Score (KSS)) and radiographs. RESULTS: Overall survival rate was 95.6% (PCR 98.4% vs. PS 92.5%), with five patients having a major revision (PCR n = 1 vs. PS n = 4, respectively). Satisfying outcome scores for both groups were described at on average 12-year follow up with no significant differences in KSS knee and function scores, WOMAC, SF-36, or Kujala scores between groups. Radiographically, there were no findings of femoral or tibial loosening or polyethylene wear in either group. CONCLUSIONS: Good long-term survival rates were described for the PCR and the PS design of an AGC TKA. There were no significant differences in clinical and radiological outcomes between a PCR and a PS design 12 years postoperatively.

MRI signal intensity of anterior cruciate ligament graft after transtibial versus anteromedial portal technique (TRANSIG): A randomised controlled clinical trial.

BACKGROUND: Two primary surgical femoral drilling techniques are used to reconstruct the anterior cruciate ligament (ACL): the transtibial (TT) technique and the anteromedial portal (AMP) technique. Currently there is no consensus on which surgical technique elicits the best clinical and functional outcomes. MRI-derived measures of the signal intensity (SI) of the ACL graft have been described as an independent predictor of graft properties. The purpose of this study was to assess MRI-derived SI measurements of the ACL graft one year after ACL reconstruction, in order to compare graft maturation of both AMP and TT ACL reconstruction techniques. METHODS: This randomised controlled trial included 33 patients admitted for primary unilateral ACL reconstruction. Primary outcome was MRI Signal intensity ratio (SIR) of the ACL graft one year after ACL reconstruction. Differences in MRI SIR were assessed on two MRI sequencies: sagittal Proton Density Turbo Spin Echo weighted images (PDTSE) and 3D T2 Gradient Echo (T2*) weighted images. Analysis of interobserver and intraobserver variability was conducted for the SIR measurements. RESULTS: No difference in signal intensity of the graft was found between the TT and AMP techniques one year after ACL reconstruction (PDTSE p = 0.665, T2* p = 0.957). Both interobserver and intraobserver variability showed strong agreement (ICC 0.64-0.94). CONCLUSION: No differences in signal intensity of the graft on MRI were seen between the femoral drilling techniques one year after ACL reconstruction, suggesting similar graft maturation at that time. Follow-up studies are needed to determine whether graft intensity changes in the long term. LEVEL OF EVIDENCE: Therapeutic study with level of evidence I.

The importance of continuous remnant preservation in anterior cruciate ligament reconstruction.

PURPOSE: Selective anteromedial or posterolateral bundle reconstruction is recognized as a treatment modality in partial anterior cruciate ligament (ACL) reconstruction (ACLR) with a biomechanically sufficient ACL remnant. However, there is paucity in literature investigating clinical outcomes of standard ACLR with preservation of residual continuous but biomechanically insufficient ACL tissue. The aim of this study was to investigate the influence of preservation of residual continuous but biomechanical insufficient ACL tissue in standard ACLR on complication and repeat surgery rate, and patient reported and clinical outcome. METHODS: The retrospective cohort comprised 134 patients (age 23 ± 7 years; Tegner 6 ± 3) with an isolated acute ACL tear. In 67 patients, residual continuous but biomechanically insufficient ACL tissue was present and preserved based on visual inspection, probing of the ACL tissue and Lachman test under arthroscopic view (standard reconstruction with tissue preservation; SRTP). These patients were matched to 67 patients that underwent ACLR where no residual ACL tissue could be preserved (standard reconstruction; SR) based on gender, age and chondral and/or meniscal status. Clinical failure (recurrent instability, pathological ACL graft laxity and/or ACL graft discontinuity), other complication and repeat-surgery rate within index surgery and 1-year and within index surgery and 2-year follow-up, and patient reported and clinical outcomes at 1-year and at 2-year follow-up were compared. RESULTS: A statistically significant lower clinical failure rate within index surgery and 1-year (SRTP, 3%; SR, 13%; P = 0.028) and within index surgery and 2-year follow-up (SRTP, 3%; SR, 23%; P = 0.001), and revision ACL surgery rate within index surgery and 1-year (SRTP, 2%; ST, 10%; P = 0.029) and within index surgery and 2-year follow-up (SRTP, 2%; SR, 18%; P = 0.001) was found in the SRTP group. No statistically significant differences were found for other investigated outcomes in patients that were without clinical failure. CONCLUSION: This study shows that in ACLR surgery, preservation of residual continuous but biomechanical insufficient ACL tissue might lead to lower clinical failure rate and ACL revision surgery rate within index surgery and 1-year, and within index surgery and 2-year follow-up compared to standard ACLR where no residual continuous ACL tissue could be preserved. LEVEL OF EVIDENCE: III.

The role of computer-assisted cryotherapy in the postoperative treatment after total knee arthroplasty: positive effects on pain and opioid consumption.

PURPOSE: The aim of this study was to investigate whether computer-assisted cryotherapy is effective in reducing postoperative pain and analgesics consumption, next to improving functional outcome and patient satisfaction after total knee arthroplasty (TKA). The hypothesis is that computer-assisted cryotherapy has positive effects on postoperative pain after TKA. METHODS: A single-centre non-blinded randomised controlled trial was designed to study the early (first postoperative week) and late (2 and 6 weeks postoperatively) additive effect of computer-assisted cooling after TKA. Participants scheduled for a TKA were randomly allocated to a cold (cryotherapy) C-group or a regular (control) R-group. Next to usual postoperative care for both groups, the C-group received computer-assisted cryotherapy during the first seven postoperative days. Primary outcome was pain, monitored with the numerical rating scale for pain and use of opioid escape medication. Secondary outcomes were function and swelling, monitored by active range of motion, timed up and go test and circumference measurements; patient-reported outcome measurements (KOOS and WORQ questionnaires); and patient satisfaction, monitored by the numerical rating scale for satisfaction. RESULTS: 102 patients participated in this study, both groups contained 51 patients. On most days during the first week, patients in the C-group scored significantly lower NRS pain scores and registered significantly less use of opioid escape medication. In a sub-analysis of 57 patients using the same standard pain protocol, patients in the C-group (n = 28) used less oxycodone during the first postoperative week. There were no significant differences between both groups in active range of motion, timed up and go, or circumference measurements. For the WORQ questionnaire, there was a significant difference between the two groups 6 weeks postoperatively in favour of the C-group. This could be however due to a reduced validity of this questionnaire shortly after TKA. The satisfaction score was not significantly different between both groups. CONCLUSION: Computer-assisted cryotherapy following TKA can be beneficial during the first postoperative week in terms of pain reduction and diminished opioid consumption. No clear differences in knee function or swelling were seen. LEVEL OF EVIDENCE: Therapeutic study with level of evidence I.

Anterolateral proximal tibial opening wedge osteotomy for biplanar correction in genu valgum recurvatum using patient specific instrumentation (PSI). A technical note.

BACKGROUND: Biplanar anterolateral proximal tibial opening wedge osteotomy has been described as successful for patients with combined recurvatum and valgus alignment. As it is a correction in two planes, it is a technically demanding procedure. We report the use of a novel technique with patient specific instrumentation (PSI) guides for different steps, aiming to reduce the complexity of this procedure. METHODS: One patient was treated for genu valgum recurvatum. A virtual surgical plan was made. A two-step PSI approach was used, consisting of an osteotomy guide and a repositioning guide and a custom trial wedges. RESULTS: Follow-up showed full function and improved VAS and KOOS scores. A neutral alignment was achieved. There was 2.76 degrees less varus compared to pre-operative planning, 1.24 degrees of excess slope and a rotational difference of 0.10 degrees. Saw plane accuracy was within 1 mm. CONCLUSIONS: PSI is a recent technical addition to HTOs as a modality to improve accuracy and reduce surgical complexity. Pre-planning and PSI use in an anterolateral opening wedge PTO allowed for an accurate and reproducible biplanar correction in genu valgum recurvatum. Accuracy was comparable to PSI use in lateral open wedge high tibial osteotomies.

Recovery Courses of Patients Who Return to Work by 3, 6 or 12 Months After Total Knee Arthroplasty.

Purpose This study compared the preoperative levels and postoperative recovery courses of physical and mental impairments, activity limitations and participation restrictions of working-age patients who return to work (RTW) by 3, 6 or 12 months after total knee arthroplasty (TKA). Methods A prospective survey study including TKA patients (aged < 65) (n = 146) who returned to work (RdTW) in the first postoperative year. Three groups were compared: those who returned by 3 (n = 35), 6 (n = 40) or 12 (n = 29) months. Surveys were completed preoperatively and at 6 weeks and 3, 6 and 12 months postoperatively. Outcomes represented domains of the International Classification of Functioning, i.e. physical impairments (pain, stiffness, vitality), mental impairments (mental health and depressive symptoms), activity limitations (physical functioning) and participation restrictions (social and work functioning). Results Preoperative knee-specific pain and physical functioning levels were better among patients who RdTW by 3 months, compared to those who returned by 12 months. Patients who RdTW by 3 months experienced significantly better recovery from physical impairments than those who returned by 6 months (on general pain) or 12 months (on general and knee-specific pain and on stiffness). Patients returning by 3 months experienced significantly better recovery from activity limitations (on knee-specific physical functioning). Conclusions To optimize return to work outcome after TKA surgery, the focus should lie on physical impairments (general and knee-specific pain, stiffness) and activity limitations (knee-specific physical functioning) during recovery.

Progression of ductal carcinoma in situ to invasive breast cancer: comparative genomic sequencing.

Several models have been described as potential mechanisms for the progression of ductal carcinoma in situ (DCIS) to invasive breast cancer (IBC). The aim of our study was to increase our understanding of DCIS progression by using massive parallel sequencing of synchronous DCIS and IBC. We included patients with synchronous DCIS and IBC (n = 4). Initially, IBC and normal tissue were subjected to whole exome sequencing. Subsequently, targeted sequencing was performed to validate those tumor-specific variants identified by whole exome sequencing. Finally, we analyzed whether those specific variants of the invasive component were also present in the DCIS component. There was a high genomic concordance between synchronous DCIS and IBC (52 out of 92 mutations were present in both components). However, the remaining mutations (40 out of 92) were restricted to the invasive component. The proportion of tumor cells with these mutations was higher in the invasive component compared to the DCIS component in a subset of patients. Our findings support the theory that the progression from DCIS to IBC could be driven by the selection of subclones with specific genetic aberrations. This knowledge improves our understanding of DCIS progression, which may lead to the identification of potential markers of progression and novel therapeutic targets in order to develop a more personalized treatment of patients with DCIS.

Nimbus: a design-driven analyses suite for amplicon-based NGS data.

Motivation: PCR-based DNA enrichment followed by massively parallel sequencing is a straightforward and cost effective method to sequence genes up to high depth. The full potential of amplicon-based sequencing assays is currently not achieved as analysis methods do not take into account the source amplicons of the detected variants. Tracking the source amplicons has the potential to identify systematic biases, enhance variant calling and improve the designs of future assays. Results: We present Nimbus, a software suite for the analysis of amplicon-based sequencing data. Nimbus includes tools for data pre-processing, alignment, single nucleotide polymorphism (SNP), insertion and deletion calling, quality control and visualization. Nimbus can detect SNPs in its alignment seeds and reduces alignment issues by the usage of decoy amplicons. Tracking the amplicons throughout analysis allows easy and fast design optimization by amplicon performance comparison. It enables detection of probable false positive variants present in a single amplicon from real variants present in multiple amplicons and provides multiple sample visualization. Nimbus was tested using HaloPlex Exome datasets and outperforms other callers for low-frequency variants. The variants called by Nimbus were highly concordant between twin samples and SNP-arrays. The Nimbus suite provides an end-to-end solution for variant calling, design optimization and visualization of amplicon-derived next-generation sequencing datasets. Availability and implementation: https://github.com/erasmus-center-for-biomics/Nimbus. Supplementary information: Supplementary data are available at Bioinformatics online.

A rare missense variant in RCL1 segregates with depression in extended families.

Depression is the most prevalent psychiatric disorder with a complex and elusive etiology that is moderately heritable. Identification of genes would greatly facilitate the elucidation of the biological mechanisms underlying depression, however, its complex etiology has proved to be a major bottleneck in the identification of its genetic risk factors, especially in genome-wide association-like studies. In this study, we exploit the properties of a genetic isolate and its family-based structure to explore whether relatively rare exonic variants influence the burden of depressive symptoms in families. Using a multistep approach involving linkage and haplotype analyses followed by exome sequencing in the Erasmus Rucphen Family (ERF) study, we identified a rare (minor allele frequency (MAF)=1%) missense c.1114C>T mutation (rs115482041) in the RCL1 gene segregating with depression across multiple generations. Rs115482041 showed significant association with depressive symptoms (N=2393, ßT-allele=2.33, P-value=1 × 10-4) and explained 2.9% of the estimated genetic variance of depressive symptoms (22%) in ERF. Despite being twice as rare (MAF<0.5%), c.1114C>T showed similar effect and significant association with depressive symptoms in samples from the independent population-based Rotterdam study (N=1604, ßT-allele=3.60, P-value=3 × 10-2). A comparison of RCL1 expression in human and mouse brain revealed a striking co-localization of RCL1 with the layer 1 interlaminar subclass of astrocytes found exclusively in higher-order primates. Our findings identify RCL1 as a novel candidate gene for depression and offer insights into mechanisms through which RCL1 may be relevant for depression.

Is a high tibial osteotomy (HTO) superior to non-surgical treatment in patients with varus malaligned medial knee osteoarthritis (OA)? A propensity matched study using 2 randomized controlled trial (RCT) datasets.

OBJECTIVE: No randomized controlled trial (RCT) has compared the high tibial osteotomy (HTO) with non-surgical treatment in patients with medial knee osteoarthritis (OA) and varus malalignment. The aim was to compare the effectiveness of an unloader brace treatment or a usual care program to the HTO regarding pain severity and knee function. DESIGN: Surgical treatment (HTO) to two non-surgical options was compared by combining the data of two RCTs. One RCT (n = 117) compared an unloader brace to usual care treatment; the other RCT (n = 92) compared closing to opening wedge HTO. One-to-many propensity score matching was used to equalize patient characteristics. We compared clinical outcome at 1 year follow-up (VAS pain (0-10) and knee function (HSS, 0-100)) with mixed model analysis. RESULTS: Propensity score matching resulted in a comparison of 30 brace patient with 83 HTO patients, and of 28 usual care patients with 71 HTO patients. Pain at 1 year after HTO (VAS 3.8) was lower than after valgus bracing (VAS 5.0) with a mean difference of -1.1 (95% CI -2.2; -0.1). Function showed a nonsignificant mean difference of 2.1 [95% CI -3.1; 7.3]. Comparing HTO to usual care a difference was seen in pain (-1.7 [95% CI -2.8; -0.6]) and function (6.6 [95% CI 0.2; 13.1]), in favor of the HTO. CONCLUSIONS: Our data suggest that HTO was more effective in pain reduction compared to both non-surgical treatments. Function improved only when HTO was compared to usual care treatment. These small differences question the benefits of surgical treatment over the brace treatment.

Progression of medial compartmental osteoarthritis 2-8 years after lateral closing-wedge high tibial osteotomy.

PURPOSE: The primary purpose of this study is to investigate the progression of medial osteoarthritis (OA) following lateral closing-wedge high tibial osteotomy (HTO). Secondary outcomes included functional and pain scores. METHODS: This prospective cohort study analysed 298 patients treated with lateral closing-wedge HTO surgery for medial compartmental OA. OA progression was measured by comparing the minimum joint space width (mJSW) and Kellgren-Lawrence (KL) score on radiographs preoperatively and postoperatively. The WOMAC score and NRS score for pain were obtained preoperatively and postoperatively to assess secondary outcomes. Failure was defined as revision surgery; survival was estimated. RESULTS: Mean follow-up was 5.2 ± 1.8 years (range 2-8.5). Mean preoperative mJSW was 3.4 ± 1.6 mm, which changed nonsignificantly (p = 0.51) to 3.4 ± 1.7 mm postoperatively. Mean annual joint space narrowing was 0.02 ± 0.34 mm/year. Progression to 1 KL grade or more was seen in 132 (44 %) patients, and annual risk of KL progression was 8.6 %. No KL progression was seen in 56 % of patients. Mean NRS decreased from 7.3 ± 1.5 to 3.5 ± 2.5 (p < 0.001). WOMAC scores decreased from 48.0 ± 17.2 to 23.6 ± 19.7 (p < 0.001). Failure was seen in 21 patients. CONCLUSION: Compared to demographic data in the literature, valgus high tibial osteotomy seems to reduce the progression of OA, reduces pain and improves knee function in patients with medial compartment OA and a varus alignment. LEVEL OF EVIDENCE: III.

Exome-sequencing in a large population-based study reveals a rare Asn396Ser variant in the LIPG gene associated with depressive symptoms.

Despite a substantial genetic component, efforts to identify common genetic variation underlying depression have largely been unsuccessful. In the current study we aimed to identify rare genetic variants that might have large effects on depression in the general population. Using high-coverage exome-sequencing, we studied the exonic variants in 1265 individuals from the Rotterdam study (RS), who were assessed for depressive symptoms. We identified a missense Asn396Ser mutation (rs77960347) in the endothelial lipase (LIPG) gene, occurring with an allele frequency of 1% in the general population, which was significantly associated with depressive symptoms (P-value=5.2 × 10-08, ß=7.2). Replication in three independent data sets (N=3612) confirmed the association of Asn396Ser (P-value=7.1 × 10-03, ß=2.55) with depressive symptoms. LIPG is predicted to have enzymatic function in steroid biosynthesis, cholesterol biosynthesis and thyroid hormone metabolic processes. The Asn396Ser variant is predicted to have a damaging effect on the function of LIPG. Within the discovery population, carriers also showed an increased burden of white matter lesions (P-value=3.3 × 10-02) and a higher risk of Alzheimer's disease (odds ratio=2.01; P-value=2.8 × 10-02) compared with the non-carriers. Together, these findings implicate the Asn396Ser variant of LIPG in the pathogenesis of depressive symptoms in the general population.

[AbstractA woman with knee pain after a fall in childhood]. / Een vrouw met kniepijn na een val op kinderleeftijd.

A 32-year-old woman presented with pain in her left knee ever since she had fallen down the stairs as a child and had landed on this knee. On the X-ray we saw two large patella fragments. We made the diagnosis of dislocated and subluxated fracture of the patella without consolidation. The previously missed fracture was treated conservatively.

Comparison of closing-wedge and opening-wedge high tibial osteotomy for medial compartment osteoarthritis of the knee: a randomized controlled trial with a six-year follow-up.

BACKGROUND: Varus deformity increases the risk of progression of medial compartment knee osteoarthritis. The aim of this study was to investigate the clinical and radiographic mid-term results of closing-wedge and opening-wedge high tibial osteotomy when used to treat this condition. METHODS: From January 2001 to April 2004, ninety-two patients were randomized to receive either a closing-wedge or an opening-wedge high tibial osteotomy. The clinical outcome and radiographic results were examined preoperatively; at one year; and, for the present study, at six years postoperatively. The outcomes that we reviewed included maintenance of the achieved correction, progression of osteoarthritis (based on the Kellgren and Lawrence classification), severity of pain (as assessed on a visual analog scale [VAS]), knee function (as measured with the Hospital for Special Surgery [HSS] score and Knee injury and Osteoarthritis Outcome Score [KOOS]), walking distance, complications, and survival with conversion to a total knee arthroplasty as the end point. The results were analyzed on the basis of the intention-to-treat principle. RESULTS: Six years postoperatively, the mean hip-knee-ankle (HKA) angle (and standard deviation) was 3.2° ± 4.1° of valgus after a closing-wedge high tibial osteotomy and 1.3° ± 5.0° of valgus after an opening-wedge high tibial osteotomy (p = 0.343). In both groups, the six-year postoperative HKA angles did not differ from the respective one-year postoperative angles. No difference in the severity of pain or in knee function was found between the two groups. Four complications (9%) occurred in the closing-wedge group and seventeen (38%), in the opening-wedge group. Ten (22%) of the patients in the closing-wedge group and three (8%) in the opening-wedge group needed conversion to a total knee arthroplasty within the six-year period (p = 0.05). The difference in the percentage of cases with conversion to total knee arthroplasty was 14% (95% confidence interval [CI] = 21.7 to 0.2). CONCLUSIONS: In the group of patients without conversion to a total knee arthroplasty, there was no difference between the high tibial closing-wedge and opening-wedge osteotomies in terms of clinical outcomes or radiographic alignment at six years postoperatively. Opening-wedge osteotomy was associated with more complications, but closing-wedge osteotomy was associated with more early conversions to total knee arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Femoral revision surgery with impaction bone grafting: 31 hips followed prospectively for ten to 15 years.

The purpose of this prospective study was to evaluate the long-term clinical and radiological outcomes of revision of the femoral component of a total hip replacement using impaction bone grafting. Femoral revision with an impacted allograft was performed on 29 patients (31 hips). In all, 21 hips (68%) had grade III or IV femoral defects according to the Endo-Klinik classification. A total of 11 patients (12 hips) died before the ten-year follow-up period. Of the remaining patients, 18 patients (19 hips) were followed for 10 to 15 years; three further patients died during this time. None of the 31 stems underwent further revision of their stem. However, four stems showed extensive subsidence (> 15 mm). One of these patients had a femoral fracture that required fixation. Three other patients had a femoral fracture, two of which required fixation and the other was treated conservatively. Patients with a femoral fracture and/or severe subsidence had significantly more grade IV defects (six of seven hips; p = 0.004). One patient needed a closed reduction for dislocation. Impaction allografting in revision hip surgery gives good long-term results for femora with grades I, II and III Endo-Klinik-classified defects. Extensive subsidence and femoral fractures were seen mainly in patients with grade IV damaged femora.

NARWHAL, a primary analysis pipeline for NGS data.

UNLABELLED: The NARWHAL software pipeline has been developed to automate the primary analysis of Illumina sequencing data. This pipeline combines a new and flexible de-multiplexing tool with open-source aligners and automated quality assessment. The entire pipeline can be run using only one simple sample-sheet for diverse sequencing applications. NARWHAL creates a sample-oriented data structure and outperforms existing tools in speed. AVAILABILITY: https://trac.nbic.nl/narwhal/.

Pitfalls in determining knee alignment: a radiographic cadaver study.

Full-length anteroposterior (AP) radiographs provide the basis for evaluating leg alignment. A cadaver study was performed to determine the effect of knee flexion and hip rotation on projected angles on full-length AP radiographs. The outcomes were verified mathematically. The results of the cadaver study were similar to the mathematical results. Flexion of the knee without rotation of the lower extremity has little effect on angles as projected on full-length AP radiographs. Rotation of the lower extremity without flexion of the knee also has little effect. Simultaneous flexion of the knee and rotation of the leg, however, cause large changes in projected angles. Full-length radiographs can be taken without fluoroscopic control as long as the knee can be fully extended. In flexion contracture, a full-length AP radiograph taken under lateral fluoroscopic control is necessary to obtain accurate determination of the mechanical axis.