Background: Cam-type femoroacetabular impingement (FAI) is a causative factor for hip pain and early hip osteoarthritis. Although cam FAI can alter hip joint biomechanics, it is unclear what role muscle forces play and how they affect the hip joint loading. Purpose/Hypothesis: The purpose was to examine the muscle contributions and hip contact forces in individuals with symptomatic cam FAI during level walking. Symptomatic cam FAI demonstrate different muscle and hip contact forces during gait. Study Design: Controlled laboratory study. Methods: Eighteen patients with symptomatic cam FAI (nFAI = 18) were age-and BMI-matched with eighteen control participants (nCON = 18). Each participant's walking kinematics and kinetics were recorded throughout a gait cycle (ipsilateral foot-strike to ipsilateral foot-off), using a motion capture system and force plates. Muscle and hip contact forces were subsequently computed using a musculoskeletal modelling program and static optimization methods. Results: The FAI group walked slower and with shorter steps; demonstrating reduced joint motions and moments during contralateral foot-strike, compared to the CON group. The FAI group showed reduced psoas major (median = 1.1, interquartile range (IQR) = 1.0-1.5 Newton/bodyweight (N/BW)) and iliacus forces (median = 1.2, IQR = 1.0-1.6 N/BW), during contralateral foot-strike, compared to the CON group (median = 1.6, IQR = 1.3-1.6 N/BW, p = 0.004; and median = 1.5, IQR = 1.3-1.6 N/BW, p = 0.03, respectively); which resulted in lower hip contact forces in the anterior (p = 0.026), superior (p = 0.02), and medial directions (p = 0.038). The three vectors produced a resultant peak force at the anterosuperior aspect of the acetabulum for both groups; with the FAI group demonstrating a substantially lower magnitude. 4 Conclusions: FAI participants altered their walking kinematics and kinetics, especially during contralateral foot-strike as a protective mechanism, and resulted in reduced psoas major and iliacus muscle force and anterosuperior hip contact force estimations. Clinical Relevance: Limited hip mobility is not only attributed to bone-on-bone impingement, caused by the cam morphology, but could be attributed to musculature as well. Not only would the psoas major and iliacus be able to protect the hip joint during flexion-extension, athletic conditioning could further strengthen core muscles for improved hip mobility and pelvic balance.

Background It is still unclear why many individuals with a cam morphology of the hip do not experience pain. It was recently reported that a decreased femoral neck-shaft angle may also be associated with hip symptoms. However, the effects that different femoral neck-shaft angles have on hip stresses in symptomatic and asymptomatic individuals with cam morphology remain unclear.Questions/purposes We examined the effects of the cam morphology and femoral neck-shaft angle on hip stresses during walking by asking: (1) Are there differences in hip stress characteristics among symptomatic patients with cam morphology, asymptomatic individuals with cam morphology, and individuals without cam morphology? (2) What are the effects of high and low femoral neck-shaft angles on hip stresses? Methods Six participants were selected, from a larger cohort, and their cam morphology and femoral neck-shaft angle parameters were measured from CT data. Two participants were included in one of three groups: (1) symptomatic with cam morphology; (2) asymptomatic with a cam morphology; and (3) asymptomatic control with no cam morphology with one participant having the highest femoral neck-shaft angle and the other participant having the lowest in each subgroup. Subject-specific finite element models were reconstructed and simulated during the stance phase, near pushoff, to examine maximum shear stresses on the acetabular cartilage and labrum. Results The symptomatic group with cam morphology indicated high peak stresses (6.3-9.5 MPa) compared with the asymptomatic (5.9-7.0 MPa) and control groups (3.8-4.0 MPa). Differences in femoral neck-shaft angle influenced both symptomatic and asymptomatic groups; participants with the lowest femoral neck-shaft angles had higher peak stresses in their respective subgroups. There were no differences among control models. Conclusions Our study suggests that the hips of individuals with a cam morphology and varus femoral neck angle may be subjected to higher mechanical stresses than those with a normal femoral neck angle. Clinical Relevance Individuals with a cam morphology and decreased femoral neck-shaft angle are likely to experience severe hip stresses. Although asymptomatic

The choice of marker set is a source of variability in motion analysis. Studies exist which assess the performance of marker sets when direct kinematics is used, but these results cannot be extrapolated to the inverse kinematic framework. Therefore, the purpose of this study was to examine the sensitivity of kinematic outcomes to inter-marker set variability in an inverse kinematic framework. The compared marker sets were plug-in-gait, University of Ottawa motion analysis model and a three-marker-cluster marker set. Walking trials of 12 participants were processed in opensim. The coefficient of multiple correlations was very good for sagittal (>0.99) and transverse (>0.92) plane angles, but worsened for the transverse plane (0.72). Absolute reliability indices are also provided for comparison among studies: minimum detectable change values ranged from 3 deg for the hip sagittal range of motion to 16.6 deg of the hip transverse range of motion. Ranges of motion of hip and knee abduction/adduction angles and hip and ankle rotations were significantly different among the three marker configurations (P < 0.001), with plug-in-gait producing larger ranges of motion. Although the same model was used for all the marker sets, the resulting minimum detectable changes were high and clinically relevant, which warns for caution when comparing studies that use different marker configurations, especially if they differ in the joint-defining markers.

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Introduction: The study’s aim was to investigate the immunohistochemical (IHC) expression of biological markers as potential prognostic/therapeutic factors in vulvar squamous cell carcinoma (VSCC). Methodology: A series of 101 patients surgically treated at our center from 2016 to 2020 were retrospectively enrolled: 53 node-negative (Group A) and 48 node-positive (Group B). A total of 146 samples, 101 from primary tumor (T) and 45 from nodal metastases (N), were investigated. The IHC panel included: p16, p53, MLH1, MSH2, MSH6, PMS2, PD-L1, CD3, HER2/neu, ER, PR, EGFR, VEGF, and CD31. The reactions were evaluated on qualitative and semi-quantitative scales. Generalized Linear Model (GLM) and cluster analysis were performed in R statistical environment. A distance plot compared the IHC panel of T with the correspondent N. Results: In Group A: p16-positive expression (surrogate of HPV-dependent pathway) was significantly higher (20.8% vs. 6.2%, p = 0.04). In Group B: PD-L1 positivity and high EGFR expression were found, respectively, in 77.1% and 97.9% patients (T and/or N). Overall, p16-negative tumors showed a higher PD-L1 expression (60.9% vs. 50.0%). In both groups: tumoral immune infiltration (CD3 expression) was mainly moderate/intense (80% vs. 95%); VEGF showed strong/moderate-diffuse expression in 13.9% of T samples; CD31, related to tumoral microvessel density (MVD), showed no difference between groups; a mutated p53 and over-expressed PD-L1 showed significant association with nodal metastasis, with Odds Ratios (OR) of 4.26 (CI 95% = 1.14–15.87, p = 0.03) and 2.68 (CI 95% = 1.0–7.19, p < 0.05), respectively; since all mismatch repair proteins (MMR) showed a retained expression and ER, PR, and HER2/neu were negative, they were excluded from further analysis. The cluster analysis identified three and four sub-groups of molecular profiles, respectively, in Group A and B, with no difference in prognosis. The molecular signature of each N and corresponding T diverged significantly in 18/41 (43.9%) cases. Conclusions: Our results support a potential role of immune checkpoint inhibitors and anti-VEGF and anti-EGFR drugs especially in patients with worse prognosis (metastatic, HPV-independent). A panel including EGFR, VEGF, PDL1, p16, and p53 might be performed routinely in primary tumor and repeated in case of lymph node metastases to identify changes in marker expression.

Background Individuals with a cam deformity and a decreased (varus) femoral neck-shaft angle may be predisposed to symptomatic femoroacetabular impingement (FAI). However, it is unclear what combined effects the cam deformity and neck angle have on acetabular cartilage and subchondral bone stresses during an impinging squat motion. We therefore used finite element analysis to examine the combined effects of cam morphology and femoral neck-shaft angle on acetabular cartilage and subchondral bone stresses during squatting, examining the differences in stress characteristics between symptomatic and asymptomatic individuals with cam deformities and individuals without cam deformities and no hip pain. Questions/purposes Using finite element analysis in this population, we asked: (1) What are the differences in acetabular cartilage stresses? (2) What are the differences in subchondral bone stresses? (3) What are the effects of high and low femoral neck-shaft angles on these stresses? Methods Six male participants were included to represent three groups (symptomatic cam, asymptomatic cam, control without cam deformity) with two participants per group, one with the highest femoral neck-shaft angle and one with the lowest (that is, most valgus and most varus neck angles, respectively). Each participant’s finite element hip models were reconstructed from imaging data and assigned subject-specific bone material properties. Hip contact forces during squatting were determined and applied to the finite element models to examine maximum shear stresses in the acetabular cartilage and subchondral bone. Results Both groups with cam deformities experienced higher subchondral bone stresses than cartilage stresses. Both groups with cam deformities also had higher subchondral bone stresses (symptomatic with high and low femoral neck-shaft angle = 14.1 and 15.8 MPa, respectively; asymptomatic with high and low femoral neck-shaft angle = 10.9 and 13.0 MPa, respectively) compared with the control subjects (high and low femoral neck-shaft angle = 6.4 and 6.5 MPa, respectively). The symptomatic and asymptomatic participants with low femoral neck-shaft angles had the highest cartilage and subchondral bone stresses in their respective subgroups. The asymptomatic participant with low femoral neck-shaft angle (123°) demonstrated anterolateral subchondral bone stresses (13.0 MPa), similar to the symptomatic group. The control group also showed no differences between cartilage and subchondral bone stresses. Conclusions The resultant subchondral bone stresses modeled here coincide with findings that acetabular subchondral bone is denser in hips with cam lesions. Future laboratory studies will expand the parametric finite element analyses, varying these anatomic and subchondral bone stiffness parameters to better understand the contributions to the pathomechanism of FAI. Clinical Relevance Individuals with a cam deformity and more varus neck orientation may experience elevated subchondral bone stresses, which may increase the risks of early clinical signs and degenerative processes associated with FAI, whereas individuals with cam morphology and normal-to-higher femoral neck-shaft angles may be at lesser risk of disease progression that would potentially require surgical intervention.