Environmental enrichment decreases anxiety-like behavior in zebrafish larvae.

The development of anxiety disorders is often linked to individuals' negative experience. In many animals, development of anxiety-like behavior is modeled by manipulating individuals' exposure to environmental enrichment. We investigated whether environmental enrichment during early ontogenesis affects anxiety-like behavior in larval zebrafish. Larvae were exposed from hatching to either an environment enriched with 3D-objects of different color and shape or to a barren environment. Behavioral testing was conducted at different intervals during development (7, 14, and 21 days post-fertilization, dpf). In a novel object exploration test, 7 dpf larvae of the two treatments displayed similar avoidance of the visual stimulus. However, at 14 and 21 dpf, larvae of the enriched environment showed less avoidance, indicating lower anxiety response. Likewise, larvae of the two treatments demonstrated comparable avoidance of a novel odor stimulus at 7 dpf, with a progressive reduction of anxiety behavior in the enriched treatment with development. In a control experiment, larvae treated before 7 dpf but tested at 14 dpf showed the effect of enrichment on anxiety, suggesting an early determination of the anxiety phenotype. This study confirms a general alteration of zebrafish anxiety-like behavior due to a short enrichment period in first days of life.

Total knee arthroplasty in the varus knee: tips and tricks.

Varus knee deformity is very common, and it can be classified according to the severity and reducibility of the deformity. Pre-operative planning is mandatory to obtain a good result. Both clinical and radiological planning should be carefully performed, particularly focused on collateral ligament deficiency. In most of the cases, a postero-stabilized implant is necessary, but in the presence of a varus thrust, a midlevel constrained (MLC) implant may be necessary. Rarely, if a severe extra-articular deformity is present, a femoral osteotomy and a high constrain implant may be necessary. In most of the cases, a standard midline approach can be performed. Soft tissue balancing is crucial, avoiding excessive releases of the medial collateral ligament (MCL). In the presence of severe deformity, more aggressive procedure such as tibial reduction osteotomy or sliding medial epicondyle osteotomy can be performed. In literature, good outcomes are reported for total knee arthroplasty (TKA) in varus deformity. In this manuscript, the available literature on TKA in varus deformity is analyzed, and the preferred surgical techniques of the authors are described.

Total knee arthroplasty in the valgus knee.

Valgus knee deformity is a challenge in total knee arthroplasty (TKA) and it is observed in nearly 10% of patients undergoing TKA. The valgus deformity is sustained by anatomical variations divided into bone remodelling and soft tissue contraction/elongation. Bone tissue variations consist of lateral cartilage erosion, lateral condylar hypoplasia and metaphyseal femur and tibial plateau remodelling. Soft tissue variations are represented by tightening of lateral structures: lateral collateral ligament, posterolateral capsule, popliteus tendon, hamstring tendons, the lateral head of the gastrocnemius and iliotibial band. Complete pre-operative planning and clinical examination are mandatory to manage bone deformities and soft tissue contractions/elongations and to decide if a higher constrained prosthesis is necessary. Two different approaches have been described to perform TKA in a valgus knee: the anteromedial approach and the anterolateral one. In valgus knee deformity bone cuts can be performed differently in order to correct low-grade deformities and reduce great deformities. There is still debate in the literature on the sequence of lateral soft tissue release to achieve the best alignment without any instability. The aim of this article is to review the anatomical variations underlying a valgus knee, to assess the best pre-operative planning and to evaluate how to choose the grade of constraint of the implant. We will also review the main approaches and surgical techniques both for bone cuts and soft tissue management. Finally, we will report on our experience and technique.

Bone marrow derived stem cells in joint and bone diseases: a concise review.

Stem cells have huge applications in the field of tissue engineering and regenerative medicine. Their use is currently not restricted to the life-threatening diseases but also extended to disorders involving the structural tissues, which may not jeopardize the patients' life, but certainly influence their quality of life. In fact, a particularly popular line of research is represented by the regeneration of bone and cartilage tissues to treat various orthopaedic disorders. Most of these pioneering research lines that aim to create new treatments for diseases that currently have limited therapies are still in the bench of the researchers. However, in recent years, several clinical trials have been started with satisfactory and encouraging results. This article aims to review the concept of stem cells and their characterization in terms of site of residence, differentiation potential and therapeutic prospective. In fact, while only the bone marrow was initially considered as a "reservoir" of this cell population, later, adipose tissue and muscle tissue have provided a considerable amount of cells available for multiple differentiation. In reality, recently, the so-called "stem cell niche" was identified as the perivascular space, recognizing these cells as almost ubiquitous. In the field of bone and joint diseases, their potential to differentiate into multiple cell lines makes their application ideally immediate through three main modalities: (1) cells selected by withdrawal from bone marrow, subsequent culture in the laboratory, and ultimately transplant at the site of injury; (2) bone marrow aspirate, concentrated and directly implanted into the injury site; (3) systemic mobilization of stem cells and other bone marrow precursors by the use of growth factors. The use of this cell population in joint and bone disease will be addressed and discussed, analysing both the clinical outcomes but also the basic research background, which has justified their use for the treatment of bone, cartilage and meniscus tissues.

How to manage a native stiff knee.

Knee stiffness is a widely known and worrying condition in several postoperative knees. Less is known about native stiff knee. The aim of this manuscript is to summarize the available literature on native stiff knee epidemiology, classification and treatment. In 1989 stiff knee was defined as a knee with less than 50° of total range of motion. If range of motion is <30°, it is defined as an ankylosed knee. Knee stiffness can be divided into three main types: flexion contractures, extension contractures, and combined contractures. Different risk factors have been associated to native stiff knee and grouped into modifiable or not modifiable. Furthermore, risk factors can be divided into patients' related no patients'-related. Different treatment modalities can be indicated to treat knee stiffness, including manipulation under anesthesia (MUA), arthroscopic and open surgical release. When stiffness is associated with articular disruption TKA represent an option. TKA in native stiff knee can be challenging for the surgeon. Implant's choice and knee exposure are the first steps. In some cases, additional release and extensive can be considered. A stepwise approach and careful preoperative planning are mandatory to obtain long-term satisfactory outcomes. Native stiff knee is a rare but invalidating condition. Different treatment modalities have been proposed as treatment. However, considering that it is frequently associated to sever arthritis, TKA can be an option in painful stiff knees. Nature of knee stiffness necessitates a customized approach to ensure successful management and achieve satisfying outcomes.

Exploring the Importance of Environmental Complexity for Newly Hatched Zebrafish.

The effects of an early impoverished social or physical environment on vertebrate neural development and cognition has been known for decades. While existing studies have focused on the long-term effects, measuring adult cognitive phenotypes, studies on the effects of environmental complexity on the early stages of development are lacking. Zebrafish (Danio rerio) hatchlings are assumed to have minimal interaction with their environment and are routinely reared in small, bare containers. To investigate the effects of being raised under such conditions on development of behaviour and cognition, hatchlings housed for 10 days in either an enriched or a standard environment underwent two cognitive tasks. The results were mixed. Subjects of the two treatments did not differ in performance when required to discriminate two areas. Conversely, we found a significant effect in a number discrimination task, with subjects from impoverished condition performing significantly worse. In both experiments, larvae reared in impoverished environment showed a reduced locomotor activity. Given the effects that enrichment appears to exert on larvae, a third experiment explored whether hatchlings exhibit a spontaneous preference for more complex environments. When offered a choice between a bare setting and one with objects of different shapes and colors, larvae spent over 70% of time in the enriched sector. Deepening these effects of an early impoverished environment on cognitive development is crucial for the welfare of captive zebrafish populations and for enhancing the quality and reliability of studies on larval zebrafish.

Mucopolysaccharidosis type II zebrafish model exhibits early impaired proteasomal-mediated degradation of the axon guidance receptor Dcc.

Most of the patients affected by neuronopathic forms of Mucopolysaccharidosis type II (MPS II), a rare lysosomal storage disorder caused by defects in iduronate-2-sulfatase (IDS) activity, exhibit early neurological defects associated with white matter lesions and progressive behavioural abnormalities. While neuronal degeneration has been largely described in experimental models and human patients, more subtle neuronal pathogenic defects remain still underexplored. In this work, we discovered that the axon guidance receptor Deleted in Colorectal Cancer (Dcc) is significantly dysregulated in the brain of ids mutant zebrafish since embryonic stages. In addition, thanks to the establishment of neuronal-enriched primary cell cultures, we identified defective proteasomal degradation as one of the main pathways underlying Dcc upregulation in ids mutant conditions. Furthermore, ids mutant fish-derived primary neurons displayed higher levels of polyubiquitinated proteins and P62, suggesting a wider defect in protein degradation. Finally, we show that ids mutant larvae display an atypical response to anxiety-inducing stimuli, hence mimicking one of the characteristic features of MPS II patients. Our study provides an additional relevant frame to MPS II pathogenesis, supporting the concept that multiple developmental defects concur with early childhood behavioural abnormalities.

Autologous cartilage fragments in a composite scaffold for one stage osteochondral repair in a goat model.

We propose a culture-free approach to osteochondral repair with minced autologous cartilage fragments loaded onto a scaffold composed of a hyaluronic acid (HA)-derived membrane, platelet-rich fibrin matrix (PRFM) and fibrin glue. The aim of the study was to demonstrate in vitro the outgrowth of chondrocytes from cartilage fragments onto this scaffold and, in vivo, the formation of functional repair tissue in goat osteochondral defects. Two sections were considered: 1) in vitro: minced articular cartilage from goat stifle joints was loaded onto scaffolds, cultured for 1 or 2 months, and then evaluated histologically and immunohistochemically; 2) in vivo: 2 unilateral critically-sized trochlear osteochondral defects were created in 15 adult goats; defects were treated with cartilage fragments embedded in the scaffold (Group 1), with the scaffold alone (Group 2), or untreated (Group 3). Repair processes were evaluated morphologically, histologically, immunohistochemically and biomechanically at 1, 3, 6 and 12 months. We found that in vitro, chondrocytes from cartilage fragments migrated to the scaffold and, at 2 months, matrix positive for collagen type II was observed in the constructs. In vivo, morphological and histological assessment demonstrated that cartilage fragment-loaded scaffolds led to the formation of functional hyaline-like repair tissue. Repair in Group 1 was superior to that of control groups, both histologically and mechanically. Autologous cartilage fragments loaded onto an HA/PRFM/fibrin glue scaffold provided a viable cell source and allowed for an improvement of the repair process of osteochondral defects in a goat model, representing an effective alternative for one-stage repair of osteochondral lesions.

Validity and reliability of the SPORTS score.

PURPOSE: Successful outcomes for an athlete usually consist of returning to their sport. The Subjective Patient Outcome for Return to Sports (SPORTS) score has been recently proposed as an easy to use score for evaluating an athlete's ability to return to their sport. The aim of this study was to test the reliability and validity of the SPORTS score in athletes 5-10 years after anterior cruciate ligament reconstruction. METHODS: A total of 47 athletes (average age 30, range 15-45), 5-10 years, after an anterior cruciate reconstruction were included in this study. Athletes were asked to complete the SPORTS score with an intermediate period of 2 weeks in order to measure reliability by using the Bland-Altman method and the ICC score. The criterion validity was assessed by calculating the Spearman correlation coefficient between the SPORTS score and Lysholm score, KOOS score and the SF-36. RESULTS: The SPORTS score showed excellent reliability (ICC = 0.967). The systematic error was 0 points (95% upper limit of agreement = 1.8 points). A strong correlation was found between the SPORTS score and the sports and recreation component on the KOOS score (r = 0.55, P < 0.001). The floor effect was 9% and the ceiling effect 32%. CONCLUSION: This study suggests that the SPORTS score is a valid and reliable tool to assess and quantify return to sport.

Optogenetic Methods to Investigate Brain Alterations in Preclinical Models.

Investigating the neuronal dynamics supporting brain functions and understanding how the alterations in these mechanisms result in pathological conditions represents a fundamental challenge. Preclinical research on model organisms allows for a multiscale and multiparametric analysis in vivo of the neuronal mechanisms and holds the potential for better linking the symptoms of a neurological disorder to the underlying cellular and circuit alterations, eventually leading to the identification of therapeutic/rescue strategies. In recent years, brain research in model organisms has taken advantage, along with other techniques, of the development and continuous refinement of methods that use light and optical approaches to reconstruct the activity of brain circuits at the cellular and system levels, and to probe the impact of the different neuronal components in the observed dynamics. These tools, combining low-invasiveness of optical approaches with the power of genetic engineering, are currently revolutionizing the way, the scale and the perspective of investigating brain diseases. The aim of this review is to describe how brain functions can be investigated with optical approaches currently available and to illustrate how these techniques have been adopted to study pathological alterations of brain physiology.

Hypothalamic Galanin-producing neurons regulate stress in zebrafish through a peptidergic, self-inhibitory loop.

Animals possess neuronal circuits inducing stress to avoid or cope with threats present in their surroundings, for instance, by promoting behaviors, such as avoidance and escape. However, mechanisms must exist to tightly control responses to stressors, since overactivation of stress circuits is deleterious for the wellbeing of an organism. The underlying neuronal dynamics responsible for controlling behavioral responses to stress have remained unclear. Here, we describe a neuronal circuit in the hypothalamus of zebrafish larvae that inhibits stress-related behaviors and prevents excessive activation of the neuroendocrine pathway hypothalamic-pituitary-interrenal axis. Central components of this circuit are neurons secreting the neuropeptide Galanin, as ablation of these neurons led to abnormally high levels of stress. Surprisingly, we found that Galanin has a self-inhibitory action on Galanin-producing neurons. Our results suggest that hypothalamic Galanin-producing neurons play an important role in fine-tuning stress responses by preventing potentially harmful overactivation of stress-regulating circuits.

Innate visual discrimination abilities of zebrafish larvae.

The ability to discriminate between objects visually plays a key role in animals' interactions with their environment because it enables them to recognise companions, prey, and predators. In the zebrafish, Danio rerio, hatching occurs early on during development (48-72 h post fertilisation), and the larvae must forage and evade predators despite their immature sensory and cognitive systems. Using a preference paradigm, we investigated whether larval zebrafish are nonetheless capable of discriminating between visual stimuli. We found that larvae discriminated not only between figures with different colours or different shapes, but also between two identical figures with different orientations and between sets of figures with different numerosities. By manipulating larvae's exposure to objects before the test, we demonstrated that their discrimination abilities are innate and do not depend upon experience. This study highlighted that zebrafish possess relatively sophisticated visual discrimination abilities even at the larval stage. These abilities likely improve larval survival via the recognition of biologically relevant stimuli.

Whole brain functional recordings at cellular resolution in zebrafish larvae with 3D scanning multiphoton microscopy.

Optical recordings of neuronal activity at cellular resolution represent an invaluable tool to investigate brain mechanisms. Zebrafish larvae is one of the few model organisms where, using fluorescence-based reporters of the cell activity, it is possible to optically reconstruct the neuronal dynamics across the whole brain. Typically, leveraging the reduced light scattering, methods like lightsheet, structured illumination, and light-field microscopy use spatially extended excitation profiles to detect in parallel activity signals from multiple cells. Here, we present an alternative design for whole brain imaging based on sequential 3D point-scanning excitation. Our approach relies on a multiphoton microscope integrating an electrically tunable lens. We first apply our approach, adopting the GCaMP6s activity reporter, to detect functional responses from retinal ganglion cells (RGC) arborization fields at different depths within the zebrafish larva midbrain. Then, in larvae expressing a nuclear localized GCaMP6s, we recorded whole brain activity with cellular resolution. Adopting a semi-automatic cell segmentation, this allowed reconstructing the activity from up to 52,000 individual neurons across the brain. In conclusion, this design can easily retrofit existing imaging systems and represents a compact, versatile and reliable tool to investigate neuronal activity across the larva brain at high resolution.

No early tibial tray loosening after surface cementing technique in mobile-bearing TKA.

Controversy still exists regarding which cementation technique of the tibial component is preferable. Full cementation showed excellent long-term outcomes, and surface cementation with fixed-bearing designs provided excellent mid-term results. Concerns have been expressed about possible rotary forces to the tibial rotating platform, when the tibial stem remains cementless, with the risk of early loosening. The purpose of this study was to evaluate the rate of early loosening and radiolucency lines in 70 consecutive unidirectional rotating platform, posterior stabilized, total knee arthroplasties, using surface cementation. Multivariate analysis was performed to identify any correlations between early loosening or radiolucency lines and clinically relevant covariates: age, sex, BMI, follow-up time, cement penetration, radiolucencies, tibial slope, femoral flexion, frontal alignment, pre-operative and post-operative Knee Scores. The tibial plateau was divided into four zones in antero-posterior view and into two zones in lateral view, and the cement penetration was evaluated in each zone. The mean follow-up was 43 months (SD 14), and the average patients' age was 73 (SD 7). The Knee Score averaged 91 (SD 8) and the Function score 86 (SD 17) at last follow-up visit. The cement penetration was >2 mm in all zones. No early loosening was detected, but in five asymptomatic patients (7%) radiolucency was noted around the tibial stem. The presence of radiolucent lines was not correlated with any of the covariates. The rate of early loosening and radiolucency lines with mobile tibial tray and surface cementation is comparable to other studies using different cementation techniques or surface cementation combined with fixed platform total knee arthroplasties.

Evaluation of tibial rotational alignment in total knee arthroplasty: a cadaver study.

Various techniques exist for establishing tibial rotational alignment during total knee arthroplasty (TKA). The purpose of this study is to establish the most precise and reproducible method to assess tibial component rotational alignment during TKA by comparing the flexion-extension technique (ROM) and the Posterior-lateral Corner Locked Technique (PLCL). Twenty posterior stabilized TKAs were performed on cadavers. The rotation angles of the tibial components obtained using the two techniques were evaluated. The tibial component rotation axis obtained using the ROM technique and the PLCL method averaged, respectively, 0.35 degrees (+ or - 4.2 degrees ) externally rotated and 0.34 degrees (+ or - 3 degrees ) internally rotated to the Akagi line. No significant differences between the two methods were found and a high correlation exists between the two techniques (Pearson's coefficient = 0.88). The ROM and PLCL techniques are both precise and reproducible methods to assess tibial component rotation during TKA. However, while the ROM technique is dependent on the correct positioning of the femoral component and the soft tissue balancing, the PCLC method is easier if a complete visualization of the posterior-lateral corner of the cut tibial plateau is achieved.

The risk of direct peroneal nerve injury using the Ranawat "inside-out" lateral release technique in valgus total knee arthroplasty.

The purposes of our study are to define a "danger zone" and a "safe zone" to avoid common peroneal nerve direct injury performing the "inside-out" release technique of posterior-lateral corner during total knee arthroplasty and to identify anatomic landmarks to localize the nerve before the soft-tissues release. Twenty cadaver dissections were used for testing. The distance from the nerve to the posterior-lateral corner of the tibia and to the posterior border of the iliotibial band averaged, respectively, 13.5 and 35.8 mm. The nerve is at risk during the release of the posterior-lateral capsule, in the triangle defined by the popliteus tendon, the tibial cut surface, and the most posterior fibers of iliotibial band (danger zone), but not during pie-crusting of the iliotibial band (safe zone).

Measuring recognition memory in zebrafish larvae: issues and limitations.

Recognition memory is the capacity to recognize previously encountered objects, events or places. This ability is crucial for many fitness-related activities, and it appears very early in the development of several species. In the laboratory, recognition memory is most often investigated using the novel object recognition test (NORt), which exploits the tendency of most vertebrates to explore novel objects over familiar ones. Despite that the use of larval zebrafish is rapidly increasing in research on brain, cognition and neuropathologies, it is unknown whether larvae possess recognition memory and whether the NORt can be used to assess it. Here, we tested a NOR procedure in zebrafish larvae of 7-, 14- and 21-days post-fertilization (dpf) to investigate when recognition memory first appears during ontogeny. Overall, we found that larvae explored a novel stimulus longer than a familiar one. This response was fully significant only for 14-dpf larvae. A control experiment evidenced that larvae become neophobic at 21-dpf, which may explain the poor performance at this age. The preference for the novel stimulus was also affected by the type of stimulus, being significant with tri-dimensional objects varying in shape and bi-dimensional geometrical figures but not with objects differing in colour. Further analyses suggest that lack of effect for objects with different colours was due to spontaneous preference for one colour. This study highlights the presence of recognition memory in zebrafish larvae but also revealed non-cognitive factors that may hinder the application of NORt paradigms in the early developmental stages of zebrafish.

Hip Spacers in Two-Stage Revision for Periprosthetic Joint Infection: A Review of Literature.

Infection after total hip arthroplasty (THA) is a devastating complication with significant consequences for patients. In literature, single and two-stage revision, irrigation and debridement, Girdlestone resection arthroplasty, and arthrodesis and amputation are reported as possible treatments. Recently, two-stage revision has become popular as the gold standard treatment for chronic hip joint infections after THA. In this review, we evaluate the current literature about microbiology of periprosthetic joint infections and the use of antibiotic-loaded cement spacers. We aim to give an overview about indications, clinical results, and mechanical complications for spacers implantation, evaluating also selection criteria, pharmacokinetic properties, and systemic safety of the most frequently used antibiotics.

Revision total knee arthroplasty (TKA): mid-term outcomes and bone loss/quality evaluation and treatment.

BACKGROUND: Revision total knee arthroplasty (rTKA) is a demanding procedure, with a high complication and failure rate and a high rate of bone losses and poor bone quality. Different classifications for bone losses have been proposed, but they do not consider bone quality, which may affect implant fixation. The aim of this study is to describe the outcomes of a consecutive series of rTKA. Furthermore, a modified bone loss classification will be proposed based also on bone quality. Finally, the association between radiolucent line (RLL) development and different risk factors will be evaluated. METHODS: All the patients who underwent rTKA between 2008 and 2016 in the same institution were included. rTKAs were performed by the same surgeon according to the three-step technique. Bone losses were classified according to the proposed classification, including bone quality evaluation. The Knee Scoring System (KSS), the Hospital for Special Surgery Knee Score (HSS), and the SF-12 were used for the clinical evaluation. Radiological evaluation was performed according to the Knee Society Roentgenographic Evaluation System. Different possible risk factors (i.e., gender, age, amount of bone losses) associated to RLL development were identified, and this association was evaluated using logistic regression. RESULTS: Fifty-one patients (53 knees) were included (60.8% female, average age 71.5 years). The average follow-up was 56.6 months (range 24-182). The most frequent cause of failure was aseptic loosening (41.5%). 18.9% of the cases demonstrated poor bone quality. Bone losses were treated according to the proposed algorithm. In all the cases, there was a significant improvement in all the scores (P < 0.05). The average post-operative range of motion was 110.5° (SD 10.7). At the radiological evaluation, all the implants resulted well aligned, with 15.1% of non-progressive RLL. There were 2 failures, with a cumulative survivorship of 92.1% at the last follow-up (SD 5.3%). At the logistic regression, none of the evaluated variables resulted associated to RLL development. CONCLUSION: rTKA is a demanding procedure, and adequate treatment of bone losses is mandatory to achieve good results. However, also bone quality should be taken into consideration when approaching bone losses, and the proposed classification may need surgeons after an adequate validation. LEVEL OF EVIDENCE: Level IV.

Medium-term follow-up of 149 mobile-bearing total knee arthroplasties and evaluation of prognostic factors influencing outcomes.

OBJECTIVE: To evaluate the medium-term outcomes of a posterior-stabilized mobile-bearing total knee arthroplasty (PS-MB-TKA) and the role of different prognostic factors. METHODS: Patients indicated for a primary cemented PS-MB-TKA between 2002 and 2010 were included and prospectively evaluated using the Knee Society Scoring System (KSS) and the Hospital for Special Surgery (HSS) knee scores. The Knee Society Roentgenographic Evaluation form was used for the radiological evaluation. Different variables were collected and divided into patient- and surgery-related. Logistic regression was used to analyze the correlation between these variables and implants outcomes and survivorship. RESULTS: In total, 149 cases were included (67.8% female, average age 70.4 years, SD ±9.4). The patella was resurfaced in 12.1% of the cases. All the implants were cemented. The average follow-up was 87.3 months (SD ±21.2). Postoperatively, there was a statistically significant improvement in all the scores. The cumulative survival was 96.2% (SD ±0.02%). At the regression analysis, female gender was associated to worse satisfaction KSS (OR = 0.26), functional KSS (OR = 0.22), and HSS (OR = 0.37) scores. Patellar resurfacing and subsequent contralateral procedures were associated to better functional KSS score (OR = 4.13, OR = 2.21), as well as varus preoperative alignment (OR = 2.12). On contrary, valgus preoperative alignment was associated to worse objective KSS score (OR = 0.23). No variables were correlated to failure or presence of radiolucent lines. CONCLUSION: Good medium-term outcomes were obtained using PS-MB-TKA, with a cumulative survivorship of 96.5%. Female gender and valgus preoperative alignment were associated to worse objective and subjective outcomes. Conversely, patellar replacement, subsequent contralateral TKA, and varus preoperative alignment were associated to better functional outcomes.