Machine Learning Applied to Pre-Operative Computed-Tomography-Based Radiomic Features Can Accurately Differentiate Uterine Leiomyoma from Leiomyosarcoma: A Pilot Study.

BACKGROUND: The accurate discrimination of uterine leiomyosarcomas and leiomyomas in a pre-operative setting remains a current challenge. To date, the diagnosis is made by a pathologist on the excised tumor. The aim of this study was to develop a machine learning algorithm using radiomic data extracted from contrast-enhanced computed tomography (CECT) images that could accurately distinguish leiomyosarcomas from leiomyomas. METHODS: Pre-operative CECT images from patients submitted to surgery with a histological diagnosis of leiomyoma or leiomyosarcoma were used for the region of interest identification and radiomic feature extraction. Feature extraction was conducted using the PyRadiomics library, and three feature selection methods combined with the general linear model (GLM), random forest (RF), and support vector machine (SVM) classifiers were built, trained, and tested for the binary classification task (malignant vs. benign). In parallel, radiologists assessed the diagnosis with or without clinical data. RESULTS: A total of 30 patients with leiomyosarcoma (mean age 59 years) and 35 patients with leiomyoma (mean age 48 years) were included in the study, comprising 30 and 51 lesions, respectively. Out of nine machine learning models, the three feature selection methods combined with the GLM and RF classifiers showed good performances, with predicted area under the curve (AUC), sensitivity, and specificity ranging from 0.78 to 0.97, from 0.78 to 1.00, and from 0.67 to 0.93, respectively, when compared to the results obtained from experienced radiologists when blinded to the clinical profile (AUC = 0.73 95%CI = 0.62-0.84), as well as when the clinical data were consulted (AUC = 0.75 95%CI = 0.65-0.85). CONCLUSIONS: CECT images integrated with radiomics have great potential in differentiating uterine leiomyomas from leiomyosarcomas. Such a tool can be used to mitigate the risks of eventual surgical spread in the case of leiomyosarcoma and allow for safer fertility-sparing treatment in patients with benign uterine lesions.

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

SUrgical Access and Pattern of Recurrence of Endometrial Cancer: The SUPeR Study, a Multicenter Retrospective Observational Study.

STUDY OBJECTIVE: To evaluate recurrence rate and pattern in apparently early-stage endometrial cancer (EC) treated with minimally invasive surgery (MIS) and compare it to the "historical" populations treated by laparotomy. Secondary outcomes were to establish if, among MIS recurrent patients, intermediate-high/high-risk patients presented the same recurrence pattern compared to those at low/intermediate-risk and to evaluate time to first recurrence (TTR) of the study population. DESIGN: Multicenter retrospective observational study. SETTING: Five Italian Gynecologic Oncology referral centers. PATIENTS: All patients with proven recurrence of apparently early-stage EC treated with MIS from January 2017 to June 2022 . The laparotomic historical cohort was obtained from Laparoscopy Compared With Laparotomy for Comprehensive Surgical Staging of Uterine Cancer: Gynecologic Oncology Group Study (LAP2) and Laparoscopic Approach to Cancer of the Endometrium trials. INTERVENTIONS: Evaluation of recurrence rate and pattern. MEASUREMENTS AND MAIN RESULTS: Seventy-seven recurrences occurred on the total of 1028 patients treated with MIS for apparently early-stage EC during a median follow-up time of 36 months. The rate of recurrence in our cohort did not differ significantly from the rate of the historical cohort (7.4% vs 7.9%, odds ratio 0.9395, 95% CI 0.6901-1.2792). No significant differences were noticed for local, abdominal, nodal, and multiple site recurrence patterns; distant site recurrence appeared more likely in patients from the historical cohort. Postoperative low/intermediate risk patients had a higher likelihood of local recurrence compared to intermediate-high/high risk patients. Mean TTR was 19 months. No significant difference of TTR was observed for each pattern of recurrence compared to others. CONCLUSION: MIS appears to be safe for the treatment of early-stage EC. We did not identify any recurrence pattern specifically associated with MIS in early-stage EC.

Spatial transcriptomics of B cell and T cell receptors reveals lymphocyte clonal dynamics.

The spatial distribution of lymphocyte clones within tissues is critical to their development, selection, and expansion. We have developed spatial transcriptomics of variable, diversity, and joining (VDJ) sequences (Spatial VDJ), a method that maps B cell and T cell receptor sequences in human tissue sections. Spatial VDJ captures lymphocyte clones that match canonical B and T cell distributions and amplifies clonal sequences confirmed by orthogonal methods. We found spatial congruency between paired receptor chains, developed a computational framework to predict receptor pairs, and linked the expansion of distinct B cell clones to different tumor-associated gene expression programs. Spatial VDJ delineates B cell clonal diversity and lineage trajectories within their anatomical niche. Thus, Spatial VDJ captures lymphocyte spatial clonal architecture across tissues, providing a platform to harness clonal sequences for therapy.

Motivation from Agency and Reward in Typical Development and Autism: Narrative Review of Behavioral and Neural Evidence.

Our ability to perform voluntary actions and make choices is shaped by the motivation from having control over the resulting effects (agency) and positive outcomes (reward). We offer an overview of distinct and common behavioral and neural signatures of agency and reward. We discuss their typical and atypical developmental trajectories, focusing on autism spectrum disorder (ASD), which is characterized by neurodiverse processes underlying action selection. We propose that reduced sensitivity to agency and reward in ASD may be related to atypical multisensory processes and motor planning, with potential for understanding restricted and repetitive behaviors. We emphasize the limitations of the existing literature, and prospects for future research. Understanding the neurocognitive processes that shape the way people with ASD select actions and perceive outcomes is essential to support not only learning, but also volition and self-determination.

Pediatric robotic surgery: issues in management-expert consensus from the Italian Society of Pediatric and Neonatal Anesthesia and Intensive Care (SARNePI) and the Italian Society of Pediatric Surgery (SICP).

BACKGROUND: Pediatric robotic-assisted surgeries have increased in recent years; however, guidance documents are still lacking. This study aimed to develop evidence-based recommendations, or best practice statements when evidence is lacking or inadequate, to assist surgical teams internationally. METHODS: A joint consensus taskforce of anesthesiologists and surgeons from the Italian Society of Pediatric and Neonatal Anesthesia and Intensive Care (SARNePI) and the Italian Society of Pediatric Surgery (SICP) have identified critical areas and reviewed the available evidence. The taskforce comprised 21 experts representing the fields of anesthesia (n = 11) and surgery (n = 10) from clinical centers performing pediatric robotic surgery in the Italian cities of Ancona, Bologna, Milan, Naples, Padua, Pavia, Perugia, Rome, Siena, and Verona. Between December 2020 and September 2021, three meetings, two Delphi rounds, and a final consensus conference took place. RESULTS: During the first planning meeting, the panel agreed on the specific objectives, the definitions to apply, and precise methodology. The project was structured into three subtopics: (i) preoperative patient assessment and preparation; (ii) intraoperative management (surgical and anesthesiologic); and (iii) postoperative procedures. Within these phases, the panel agreed to address a total of 18 relevant areas, which spanned preoperative patient assessment and patient selection, anesthesiology, critical care medicine, respiratory care, prevention of postoperative nausea and vomiting, and pain management. CONCLUSION: Collaboration among surgeons and anesthesiologists will be increasingly important for achieving safe and effective RAS procedures. These recommendations will provide a review for those who already have relevant experience and should be particularly useful for those starting a new program.

Transnasal Endoscopic Approach for Osteoid Osteoma of the Odontoid Process in a Child: Technical Note and Systematic Review of the Literature.

Osteoid osteoma (OO) is a primary benign tumor that accounts for up to 3% of all bone tumors. The cervical spine is less affected by OOs, and very few cases of C2 OOs have been reported in the literature, both in adults and children. Surgery may be required in case of functional torticollis, stiffness, and reduced range of motion (ROM) due to cervical OOs refractory to medical therapy. Several posterior and anterior surgical techniques have been described to remove C2 OOs. In particular, anterior approaches to the cervical spine represent the most used surgical route for treating C2 OOs. We describe the first case of OO of the odontoid process removed through a transnasal endoscopic approach with the aid of neuronavigation in a 6-year-old child. No intraoperative complications occurred, and the post-operative course was uneventful. The patient had immediate relief of neck pain and remained pain-free throughout the follow-up period, with complete functional recovery of the neck range of motion (ROM). In this case, based on the favorable anatomy, the transnasal endoscopic approach represented a valuable strategy for the complete removal of an anterior C2 OO without the need for further vertebral fixation since the preservation of ligaments and paravertebral soft tissue.

Prostate cancer disease recurrence after radical prostatectomy is associated with HLA type and local cytomegalovirus immunity.

Prostate cancer is a heterogeneous disease with a need for new prognostic biomarkers. Human leukocyte antigen (HLA) genes are highly polymorphic genes central to antigen presentation to T-cells. Two alleles, HLA-A*02:01 and HLA-A*24:02, have been associated with prognosis in patients diagnosed with de novo metastatic prostate cancer. We leveraged the next-generation sequenced cohorts CPC-GENE and TCGA-PRAD to examine HLA alleles, antiviral T-cell receptors and prostate cancer disease recurrence after prostatectomy. Carrying HLA-A*02:01 (111/229; 48% of patients) was independently associated with disease recurrence in patients with low-intermediate risk prostate cancer. HLA-A*11 (carried by 42/441; 10% of patients) was independently associated with rapid disease recurrence in patients with high-risk prostate cancer. Moreover, HLA-A*02:01 carriers in which anti-cytomegalovirus T-cell receptors (CMV-TCR) were identified in tumors (13/144; 10% of all patients in the cohort) had a higher risk of disease recurrence than CMV-TCR-negative patients. These findings suggest that HLA-type and CMV immunity may be valuable biomarkers for prostate cancer progression.

"Clock mapping" prior to excisional surgery in vulvar Paget's disease: tailoring the surgical plan.

INTRODUCTION: Paget disease is a rare neoplasm of the skin that mainly involves the vulvar region. Vulvar Paget's disease (VPD) can spread beyond the apparent edges of the lesion resulting in a high risk of involved surgical margins. Our aim is to verify the efficacy of a preoperative vulvo-vaginal intensive clock mapping in the prediction of the invasiveness and the extension of VPD. MATERIALS AND METHODS: All consecutive patients with primary VPD referred to our institution from July 2005 to December 2018 were subjected to a preoperative intensive biopsy mapping (clock mapping) of the vulvo-vaginal area: inside and outside the vulvar skin visible lesion, according to o'clock positions, and in the vagina. Patients with positive biopsies "only inside" or "also beyond" the visible lesion were included, respectively, in Group A and B. Surgical excision was drawn passing by the points with negative histology. Pathological findings of mapping biopsies were compared with those from radical surgery. RESULTS: A total of 28 women were enrolled. After clock mapping definitive histology: 17 (60.7%) and 11 (39.3%) patients were included in Group A and B. Definitive histology showed non-invasive, micro-invasive and invasive VPD, respectively, in 13 (46.4%), 11 (39.3%) and 4 (14.3%) patients, with 4 patients further upstaged. Overall, negative margins were found in 14 (50%) patients: 9 (32.1%) from Group A and 5 (17.9%) from Group B. In 23 cases (82.1%), clock mapping identified free surgical margins along the vulvo-perineal skin excision front. CONCLUSIONS: Preoperative clock mapping emerged as potentially useful workup tool to predict invasiveness and extension of VPD, to tailor surgical excision.

The Vulvar Immunohistochemical Panel (VIP) Project: Molecular Profiles of Vulvar Squamous Cell Carcinoma.

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.

The vulvar immunohistochemical panel (VIP) project: molecular profiles of vulvar Paget's disease.

PURPOSE: To investigate the expression of biological markers in primary vulvar Paget's disease (VPD). METHODS: Forty-one patients referred to a single major Center for Gynecologic Oncology from January 2008 to June 2018 were enrolled retrospectively: 30 non-invasive-VPD and 11 invasive-VPD. A total number of 60 samples, from all the 41 vulvar sites (VS), 8 metastatic lymph node sites (MLS) and 11 successive recurrent disease in vulvar site (RVS), were tested for an immunohistochemical panel, including the following markers: PD-L1, CD3, MSH2, MSH6, MLH1, PMS2, HER2/neu, EGFR, p16, p53, Ki67, ER, PR, AR, VEGF and CD31. RESULTS: We found a positive PD-L1 in 10% of non-invasive-VPD and 27% of invasive-VPD (18% VS; 38% MLS). ER and AR were expressed respectively in more than 70% and 75% of all specimens. HER2/neu amplification was found in 21% of non-invasive-VPD and 45% of invasive-VPD (40% VS; 38% MLS). A machine learning cluster analysis identified three groups among non- invasive-VPD: cluster-1 with higher median ER expression (40%); cluster-3 with more frequent HER2/neu overexpression (46%). Among invasive-VPD, two clusters were found: the second with more frequent HER2/neu overexpression (67% vs. 0%) and nodal metastases (100% vs. 25%). Repeating the IHC panel on the correspondent MLS and RVS, it significantly changed, respectively, in 50% and 27%. CONCLUSIONS: This study reveals the expression of PDL-1 and ER and confirms the expression of HER2/AR in VPD; new bases are provided to design multicenter clinical trials on personalized target therapies.

Reviewing vulvar Paget's disease molecular bases. Looking forward to personalized target therapies: a matter of CHANGE.

OBJECTIVES: To review the published literature on vulvar Paget's disease (VPD) molecular bases, aiming to support the need for tailored treatment in women affected by this 'orphan' tumor. METHODS: MEDLINE-PubMed and Scopus were interrogated using the following algorithm: (extramammary OR extra mammary OR vulvar) AND (paget OR pagets OR paget's) AND (molecular OR biological OR marker OR protein OR target OR expression). The inclusion criteria for papers were: peer-reviewed English-language journals, articles published in the last 30 years, studies focused on fixed research questions, quality assessment on the basis of the relevance and contribution to the selected topics. RESULTS: A total of 42 studies were selected, providing the following results. Molecular markers implicated in cell cycle transitions seem to be related to prognosis and could help to tailor conventional treatments. Fragmented but consistent preliminary data exist on hormonal receptor expression, ERBB2 amplification/overexpression and abnormal vascular proliferation, offering a concrete possibility for target therapy trials. Conversely, other fields linked to the possible use of immunotherapy are currently relatively unexplored, such as the tumor 'immune contexture', programmed death ligand-1 (PD-L1) expression and defects in the mismatch repair system, which is involved in genomic instability and potentially promotes a consistent response to treatment. CONCLUSIONS: Additional effort is needed to further characterize these aspects. Centralization of patients in dedicated units would be beneficial for concentrating patient numbers, collecting valuable clinical data and conducting clinical trials. Interdisciplinary study platforms should be developed and integrated into wider multicentric networks.

Cam FAI and Smaller Neck Angles Increase Subchondral Bone Stresses During Squatting: A Finite Element Analysis.

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.

Altered Walking and Muscle Patterns Reduce Hip Contact Forces in Individuals With Symptomatic Cam Femoroacetabular Impingement.

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. Patients with symptomatic cam FAI would demonstrate different muscle and hip contact forces during gait. STUDY DESIGN: Controlled laboratory study. METHODS: Eighteen patients with symptomatic cam FAI were matched for age and body mass index with 18 control participants. Each participant's walking kinematics and kinetics were recorded throughout a gait cycle (ipsilateral foot-strike to ipsilateral foot-off) by use of a motion capture system and force plates. Muscle and hip contact forces were subsequently computed by use of a musculoskeletal modeling 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 with the control group. The FAI group showed reduced psoas major (median, 1.1 newtons per bodyweight [N/BW]; interquartile range [IQR], 1.0-1.5 N/BW) and iliacus forces (median, 1.2 N/BW; IQR, 1.0-1.6 N/BW), during contralateral foot-strike, compared with the control group (median, 1.6 N/BW; IQR, 1.3-1.6 N/BW, P = .004; and median, 1.5 N/BW; IQR, 1.3-1.6 N/BW, P = .03, respectively), which resulted in lower hip contact forces in the anterior ( P = .026), superior ( P = .02), and medial directions ( P = .038). The 3 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. CONCLUSION: FAI participants altered their walking kinematics and kinetics, especially during contralateral foot-strike, as a protective mechanism, which resulted in reduced psoas major and iliacus muscle force and anterosuperior hip contact force estimations. CLINICAL RELEVANCE: Limited hip mobility not only is attributed to bone-on-bone impingement, caused by 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.

Increased Hip Stresses Resulting From a Cam Deformity and Decreased Femoral Neck-Shaft Angle During Level Walking.

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 participants with cam morphology had elevated stresses, a higher femoral neck-shaft angle was associated with lower stresses. Future research should examine larger amplitudes of motion to assess adverse subchondral bone stresses.

How Different Marker Sets Affect Joint Angles in Inverse Kinematics Framework.

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.

Regression models to predict hip joint centers in pathological hip population.

The purpose was to investigate the validity of Harrington's and Davis's hip joint center (HJC) regression equations on a population affected by a hip deformity, (i.e., femoroacetabular impingement). Sixty-seven participants (21 healthy controls, 46 with a cam-type deformity) underwent pelvic CT imaging. Relevant bony landmarks and geometric HJCs were digitized from the images, and skin thickness was measured for the anterior and posterior superior iliac spines. Non-parametric statistical and Bland-Altman tests analyzed differences between the predicted HJC (from regression equations) and the actual HJC (from CT images). The error from Davis's model (25.0 ± 6.7 mm) was larger than Harrington's (12.3 ± 5.9 mm, p<0.001). There were no differences between groups, thus, studies on femoroacetabular impingement can implement conventional regression models. Measured skin thickness was 9.7 ± 7.0mm and 19.6 ± 10.9 mm for the anterior and posterior bony landmarks, respectively, and correlated with body mass index. Skin thickness estimates can be considered to reduce the systematic error introduced by surface markers. New adult-specific regression equations were developed from the CT dataset, with the hypothesis that they could provide better estimates when tuned to a larger adult-specific dataset. The linear models were validated on external datasets and using leave-one-out cross-validation techniques; Prediction errors were comparable to those of Harrington's model, despite the adult-specific population and the larger sample size, thus, prediction accuracy obtained from these parameters could not be improved.

Comparison of total hip arthroplasty surgical approaches by Principal Component Analysis.

Gait adaptations are persistent after total hip arthroplasty and can depend on the type of surgery. This study focused on two surgical approaches: anterior and lateral. To analyze gait adaptations, biomechanical analyses usually employ an a priori selection of the parameters that leads to incomplete or redundant information. In contrast, Principal Component Analysis (PCA) provides an efficient transformation of the dataset by automatically identifying the major sources of variability. The purpose of this study was to investigate differences in level-walking among three groups of participants using PCA: patients undergoing an anterior surgical approach, patients undergoing a lateral surgical approach, and healthy controls. Biomechanical descriptions of the extracted principal components aided in the interpretation of the statistically significant results obtained from multivariate analysis of covariance (MANCOVA) tests. A point system was introduced to summarize the results and guide the interpretation. PCA captured reduced magnitude in sagittal and frontal moments in the anterior approach group, and reduced sagittal peaks angle in the lateral group, as previously found with traditional analyses. PCA also identified significant pattern delays in the anterior group, unnoticed in previous studies. In conclusion, neither surgical approach restored normal gait functionality because lower extremity kinetics and kinematics alterations persisted at 300-day follow-up after the surgery, regardless of the technique.

Automated software for analysis of ciliary beat frequency and metachronal wave orientation in primary ciliary dyskinesia.

Patients with primary ciliary dyskinesia (PCD) have structural and/or functional alterations of cilia that imply deficits in mucociliary clearance and different respiratory pathologies. A useful indicator for the difficult diagnosis is the ciliary beat frequency (CBF) that is significantly lower in pathological cases than in physiological ones. The CBF computation is not rapid, therefore, the aim of this study is to propose an automated method to evaluate it directly from videos of ciliated cells. The cells are taken from inferior nasal turbinates and videos of ciliary movements are registered and eventually processed by the developed software. The software consists in the extraction of features from videos (written with C++ language) and the computation of the frequency (written with Matlab language). This system was tested both on the samples of nasal cavity and software models, and the results were really promising because in a few seconds, it can compute a reliable frequency if compared with that measured with visual methods. It is to be noticed that the reliability of the computation increases with the quality of acquisition system and especially with the sampling frequency. It is concluded that the developed software could be a useful mean for PCD diagnosis.