Surgical factors play a critical role in predicting functional outcomes using machine learning in robotic-assisted total knee arthroplasty.

PURPOSE: Predictive models help determine predictive factors necessary to improve functional outcomes after total knee arthroplasty (TKA). However, no study has assessed predictive models for functional outcomes after TKA based on the new concepts of personalised surgery and new technologies. This study aimed to develop and evaluate predictive modelling approaches to predict the achievement of minimal clinically important difference (MCID) in patient-reported outcome measures (PROMs) 1 year after TKA. METHODS: Four hundred thirty robotic-assisted TKAs were analysed in this retrospective study. The mean age was 67.9 ± 7.9 years; the mean body mass index (BMI) was 32.0 ± 6.8 kg/m2. The following PROMs were collected preoperatively and 1-year postoperatively: knee injury and osteoarthritis outcome score for joint replacement, Western Ontario and McMaster Universities osteoarthritis index (WOMAC) Function, WOMAC Pain. Demographic data, preoperative CT scan, implant size, implant position on the robotic system and characteristics of the joint replacement procedure were selected as predictive variables. Four machine learning algorithms were trained to predict the MCID status at 1-year post-TKA for each PROM survey. 'No MCID' was chosen as the target. Models were evaluated by class discrimination (F1-score) and area under the receiver operating characteristic curve (ROC-AUC). RESULTS: The best-performing model was ridge logistic regression for WOMAC Function (area under the curve [AUC] = 0.80, F1 = 0.48, sensitivity = 0.79, specificity = 0.62). Variables most strongly contributing to not achieving MCID status were preoperative PROMs, high BMI and femoral resection depth (posterior and distal), supporting functional positioning principles. Conversely, variables contributing to a positive outcome (achieving MCID) were medial/lateral alignment of the tibial component, whether the procedure was an outpatient surgery and whether the patient received managed Medicare insurance. CONCLUSION: The most predictive variables included preoperative PROMs, BMI and surgical planning. The surgical predictive variables were valgus femoral alignment and femoral rotation, reflecting the benefits of personalised surgery. Including surgical variables in predictive models for functional outcomes after TKA should guide clinical and surgical decision-making for every patient. LEVEL OF EVIDENCE: Level III.

True Confessions of Neutral Mechanical Disciple-How I Learned to Love a Patient-Specific Target.

INTRODUCTION: Classical neutral mechanical alignment in total knee arthroplasty (TKA) has been a standard paradigm, while more recently, other alignment schemas, such as kinematic, individualized, and functional, have been explored. This study aimed to investigate the effect of three-dimensional (3D) computed tomography (CT)-based surgical robotics inputs on a classically trained surgeon's TKA component positions and alignment targets over time. MATERIALS AND METHODS: Data from 1,394 consecutive robotically-assisted TKAs by a single surgeon from 2016 to 2020 were analyzed. Metrics collected included pre-balance planned implant component positions, final planned implant component positions after soft tissue balancing, and constitutional alignment from CT scans. Joint line obliquity was plotted against the arithmetic hip-knee angle (aHKA) using coronal plane alignment of the knee (CPAK). Three categories of alignment strategy were defined: true mechanical alignment (tMA), adjusted mechanical alignment (aMA), and no mechanical alignment (noMA). RESULTS: A shift to overall varus component positioning was observed over the years. Joint line obliquity according to CPAK showed a wider spread in later years, and the distribution of tibial and femoral coronal alignment angles expanded over time. CONCLUSION: The study revealed a change in alignment targets and final positioning of components away from neutral biomechanical axes in a large volume of TKAs by a single, classically trained surgeon over five years of using a robotic arm-assisted TKA system with CT-based planning. The most dominant factor for this change was the use of 3D CT planning, allowing the surgeon to assess patient-specific anatomy and plan accordingly. Outcome data is needed to determine if this change in behavior and surgical technique was beneficial. In summary, using a CT scan-based robotically assisted technique led to a gradual and complete shift from tMA to predominantly a non-mechanically aligned philosophy in TKA.

The effect of mutations in the lid region of Thermomyces lanuginosus lipase on interactions with triglyceride surfaces: A multi-scale simulation study.

Lipases naturally function at the interface formed between amphiphilic molecules and the aqueous environment. Thermomyces lanuginosus lipase (TLL) is a well-characterised lipase, known to exhibit interfacial activation during which a lid region covering the active site becomes displaced upon interaction with an interface. In this study, we investigate the effect the amino acid sequence of the lid region on interfacial binding and lid dynamics of TLL. Three TLL variants were investigated, a wild-type variant, a variant containing an esterase lid region (Esterase), and a Hybrid variant, containing both wild-type lid residues and esterase lid residues. Multiple coarse-grained molecular dynamics simulations revealed that the interfacial binding orientation of TLL was significantly affected by the nature of amino acids in the lid region, and atomistic simulations indicated effects on the structural dynamics of the lid itself. The atomistic simulations, as well as steered molecular dynamics simulations, also indicated that the Esterase lid region was less flexible than the wild-type lid region, whereas the Hybrid variant displayed superior lid flexibility and stability in the open conformation both at the interface, and in aqueous solution. Additional experiments performed to investigate the activity and binding behaviour of the lipase variants indicated a slightly higher specific activity for the Hybrid variant compared to the wild-type variant, correlating the observations of increased lid flexibility. Together, these results are in line with previous experimental studies, highlighting the importance of the nature of the amino acid residues within the functional lid region of lipases, particularly regarding interfacial binding orientation, activation, and structural stability.

Biomimetic Phospholipid Membrane Organization on Graphene and Graphene Oxide Surfaces: A Molecular Dynamics Simulation Study.

Supported phospholipid membrane patches stabilized on graphene surfaces have shown potential in sensor device functionalization, including biosensors and biocatalysis. Lipid dip-pen nanolithography (L-DPN) is a method useful in generating supported membrane structures that maintain lipid functionality, such as exhibiting specific interactions with protein molecules. Here, we have integrated L-DPN, atomic force microscopy, and coarse-grained molecular dynamics simulation methods to characterize the molecular properties of supported lipid membranes (SLMs) on graphene and graphene oxide supports. We observed substantial differences in the topologies of the stabilized lipid structures depending on the nature of the surface (polar graphene oxide vs nonpolar graphene). Furthermore, the addition of water to SLM systems resulted in large-scale reorganization of the lipid structures, with measurable effects on lipid lateral mobility within the supported membranes. We also observed reduced lipid ordering within the supported structures relative to free-standing lipid bilayers, attributed to the strong hydrophobic interactions between the lipids and support. Together, our results provide insight into the molecular effects of graphene and graphene oxide surfaces on lipid bilayer membranes. This will be important in the design of these surfaces for applications such as biosensor devices.

Treatment of anal dysplasia in HIV-positive men who have sex with men in a large AIDS reference centre.

OBJECTIVES: Over the last few decades, incidence of anal cancer among HIV-positive men has been on the rise. In this context, programmes of screening and treatment of anal dysplasia which is a precursor of anal cancer have been developed. The aim of our study was to describe the efficiency, side effects and outcome of anal dysplasia treatment in a population of HIV-positive men who have sex with men (MSM). METHODS: We performed a retrospective study of HIV-positive MSM who received treatment for anal dysplasia between May 2010 and February 2014 in the Saint-Pierre University Hospital, Brussels. The different treatments used were electrocautery (ECA), infrared coagulation (IRC), surgical treatment and imiquimod. RESULTS: Seventy-three HIV-infected MSM were included in the study, counting 62% of HGAIN. Median age was 41 years. Eighty-one per cent were on HAART. Median CD4 cell count was 525 cell/mm³, and 65% had undetectable viral loads. A total of 139 therapeutic interventions were recorded during the study period, and two-thirds of the enrolled patients received more than one treatment. At 540 days of follow-up, the rate of treatment response was 62%. Fifty per cent of the persistent HGAIN were metachronous lesions. No severe adverse events were recorded but frequent treatment-associated discomfort was reported, such as pain, self-limited bleeding, infection and anal irritation. CONCLUSION: Treatment of anal dysplasia appears to be safe and to offer short-term efficiency. However, its long-term efficiency remains unknown, especially in the HIV-positive population in which spontaneous clearance is lower and rate of recurrence higher.

Interfacial activation of M37 lipase: A multi-scale simulation study.

Lipases are enzymes of biotechnological importance that function at the interface formed between hydrophobic and aqueous environments. Hydrophobic interfaces can induce structural transitions in lipases that result in an increase in enzyme activity, although the detailed mechanism of this process is currently not well understood for many lipases. Here, we present a multi-scale molecular dynamics simulation study of how different interfaces affect the conformational dynamics of the psychrophilic lipase M37. Our simulations show that M37 lipase is able to interact both with anionic lipid bilayers and with triglyceride surfaces. Interfacial interactions with triglyceride surfaces promote large-scale motions of the lid region of M37, spanning residues 235-283, revealing an entry pathway to the catalytic site for substrates. Importantly, these results suggest a potential activation mechanism for M37 that deviates from other related enzymes, such as Thermomyces lanuginosus lipase. We also investigated substrate binding in M37 by using steered MD simulations, confirming the open state of this lipase. The exposure of hydrophobic residues within lid and active site flap regions (residues 94-110) during the activation process provides insights into the functional effect of hydrophobic surfaces on lipase activation.

Women's desire for children in an HIV population: a clinical pilot study in Burkina Faso.

INTRODUCTION: Today, thanks to the HAART, HIV has become a chronic disease. In most cases, HIV positive women are of reproductive age and at present, the vertical transmission rate is around 0.1% for women with an undetectable viral load. So, it is normal that the question of seropositive women's desire to have children is on the table. METHODS: In this experimental study, 50 HIV-seropositive and 44 seronegative women were interviewed about their desire to have children. Some of the questions asked were: "How many children did you want to have before you got married/at 15 years of age if you aren't married?" "How many children would you like to have today, considering your present situation?". In case of a difference between "before" and "now", we asked them: "What are the reasons for this difference?". This study was performed in Burkina Faso. RESULTS: The positive women tend to desire more children "before" and fewer children "now" than negative women (OR: 1.33; C.I. 95%: 0.86-2; p= 0.19 vs OR: 0.78; C.I. 95%: 0.51-1.21; p= 0.27). 62% of HIV positive women mention multiple reasons directly linked to their seropositivity to explain the difference between "before" and "now". 70% of HIV positive women still want to have children. We have noted that the positive women who still want children are more likely to be younger (p < 0.05 by Two-Sample T tests), in a relationship (p < 0.01 by Chi-Square Test) and to have been diagnosed earlier than the positive women who don't want any children (p=0.01 by Wilcoxon Rank Sum Test). CONCLUSION: Even if the results of this pilot study are preliminary, they show that HIV positive and negative women have a relatively similar desire for children, even though seropositive women seem to want fewer children than their uninfected counterparts. Most of the reasons which reduce HIV positive women's desire to have children are directly linked to HIV. This is why getting these women informed about materno-fetal transmission risks and existing treatments is really important to give them the opportunity to make a conscious choice.