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PURPOSE: To evaluate the concomitant pathology in recalcitrant LE using MRI with arthroscopic finding correlation. METHODS: A total of 49 patients were diagnosed with chronic recalcitrant LE and divided into two: LCL complex-intact and LCL complex-involved groups by evaluating MRI as confirmed by a radiologist. Patient information for the history of steroid injection and symptom duration was extracted from the medical records. Arthroscopic images taken during arthroscopic extensor carpi radialis brevis release were evaluated to assess the quality of lateral capsule and concomitant plica. RESULTS: A total of 24 and 25 patients were included in the LCL-intact and LCL-involved groups, respectively. Among them, seven had complete RCL tears recorded in the LCL-involved group. Symptom duration (15 ± 9 vs. 22 ± 13, p = 0.029) and the number of steroid injections (3 ± 2 vs. 5 ± 3, p = 0.040) were significantly higher in the LCL-involved group than that in the LCL-intact group. A capsular tear was detected for 5 (20%) patients in the LCL-intact and 14 (56%) in the LCL-involved group (p = 0.027). Concomitant plica was observed in 15 (62%) patients in LCL-intact and seven (28%) in the LCL-involved group (p = 0.015). RC joint widening was observed in four patients in the LCL-involved group. CONCLUSION: The recalcitrant LE is highly a concomitant pathology including LCL complex insufficiency and pathologic elbow plica lesion. The risk factors of LCL insufficiency associated with refractory LE may include multiple steroid injections. Arthroscopic finding such as capsular tears and elbow drive-through signs can be suspected signs for LCL complex insufficiency.

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The construction models of smart cities and low-carbon cities are crucial for advancing global urbanization, enhancing urban governance, and addressing major urban challenges. Despite significant advancements in smart and low-carbon city research, a consensus on their coupling coordination remains elusive. This study employs mixed-method research, combining qualitative and quantitative analyses, to investigate the coupling coordination between urban smart performance (SCP) and low-carbon level (LCL) across 52 typical smart and low-carbon pilot cities in China. Independent evaluation models for SCP and LCL qualitatively assess the current state of smart and low-carbon city construction. Additionally, an Entropy-TOPSIS-Pearson correlation-Coupling coordination degree (ETPC) analysis model quantitatively examines their relationship. The results reveal that smart city initiatives in China significantly outperform low-carbon city development, with notable disparities in SCP and LCL between eastern, non-resource-based, and central cities versus western, resource-dependent, and peripheral cities. A strong positive correlation exists between urban SCP and overall LCL, with significant correlations in management, society, and economy, and moderate to weak correlations in environmental quality and culture. As SCP levels improve, the coupling coordination degree between the urban SCP and LCL systems also increases, driven primarily by economic, management, and societal factors. Conversely, the subsystems of low-carbon culture and environmental quality show poorer integration. Based on these findings, this study proposes an evaluation system for smart and low-carbon coupling coordination development, outlining pathways for future development from the perspective of urban complex systems.

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Lymphoblastoid cell lines (LCLs) are immortalised peripheral B lymphocytes, transformed via infection with Epstein Barr virus (EBV). The use of LCLs to study B cell function remains controversial and core markers to define physiological B cell populations are not consistent between studies of physiological B cells and LCLs. A consensus on the nature of these commonly used cell lines has not been reached. Recently, a core set of markers to subtype peripheral B cells was proposed, addressing the lack of agreed markers for B cell characterisation. In this present study, the consensus panel was applied to describe the B cell subtypes in LCLs. We found that LCLs were generally not physiologically representative of B cells, with most cells harbouring marker combinations absent on peripheral B cells. Some B cell subtyping markers were fundamentally altered during EBV transformation to LCLs (e.g. CD19, CD21). Notably, most LCLs secreted IgG but the associated marker combinations were predominantly only present in vitro following EBV transformation. This study therefore informs interpretation of past investigations, and planning of future studies using LCLs, as these cells are unlikely to behave like their pre-transformed B cell subtype.

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During evolution, new open reading frames (ORFs) with the potential to give rise to novel proteins continuously emerge. A recent compilation of noncanonical ORFs with translation signatures in humans has identified thousands of cases with a putative de novo origin. However, it is not known which is their distribution in the population. Are they universally translated? Here, we use ribosome profiling data from 65 lymphoblastoid cell lines from individuals of Yoruba origin to investigate this question. We identify 2,587 de novo ORFs translated in at least one of the cell lines. In line with their de novo origin, the encoded proteins tend to be smaller than 100 amino acids and encode positively charged proteins. We observe that the de novo ORFs are more polymorphic in the population than the set of canonical proteins, with a substantial fraction of them being translated in only some of the cell lines. Remarkably, this difference remains significant after controlling for differences in the translation levels. These results suggest that variations in the level translation of de novo ORFs could be a relevant source of intraspecies phenotypic diversity in humans.

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Introduction: The varus and valgus knee deformities result from imbalance in tension between medial and lateral soft tissue compartments. These conditions need to be addressed during total knee arthroplasty (TKA). However, there is no consensus on optimal soft-tissue release techniques for correcting varus and valgus deformities during TKA. We assessed the efficacy of a novel grid-based pie-crusting technique on soft-tissue release. Methods: Cadaver knees were dissected, leaving only the femur and tibia connected by an isolated MCL or the femur and fibula connected by an isolated LCL. Bone cuts were made as performed during primary TKA. Mechanical testing was performed using an MTS machine. A 3D-printed 12-hole grid was placed directly over the MCL and LCL. Using an 18-gauge needle, horizontal in-out perforations were made 3 mm apart. Deformation and stiffness of the ligaments were collected after every 2 perforations. Means were calculated, and regression analyses were performed. Results: A total of 7 MCL and 6 LCL knees were included in our analysis. The mean medial femorotibial (MFT) space increased from 6.018 ± 1.4 mm-7.078 ± 1.414 mm (R2 = 0.937) following 12 perforations. The mean MCL stiffness decreased from 32.15 N/mm-26.57 N/mm (R2 = 0.965). For the LCL group, the mean gap between the femur and fibula increased from 4.287 mm-4.550 mm following 8 perforations. The mean LCL stiffness decreased from 29.955 N/mm-25.851 N/mm. LCL stiffness displayed a strong inverse relationship with the number of holes performed (R2 = 0.988). Discussion: Our results suggest that using this novel grid for pie-crusting of the MCL and LCL allows for gradual lengthening of the ligaments without sacrificing their structural integrity. Our proposed technique may serve as a valuable piece in the soft-tissue release toolkit for orthopaedic surgeons performing TKA in varus and valgus deformed knees.

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Association of lightning with Lifting Condensation Level (LCL), Equilibrium Level (EL), K Index, and humidity at 850 mb and 200 mb in 2019 and 2020 over National Capital Region (Delhi) (Lat: 27°N -29°N, Lon: 76°E-78°E) is investigated using in-situ observation data. Study shows high lightning activity during low LCL, and vice versa. This high lighting and low LCL is associated with high relative humidity at 850 mb, and high "K" index. Low LCL and high relative humidity (low dew point depression) at 850 mb helps in generating super cell thunderstorms with spinning/tornado updraft. It is seen that asymmetric LCL height and relative humidity at 850 mb is the prime causes for uneven seasonal lightning in 2019 and 2020 over the region, despite more or less same seasonal aerosol and relative humidity. Anvil clouds behave uneven with time, despite, unanimous cloud top glaciation.

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BACKGROUND: Current evidence suggests that cis-regulatory elements controlling gene expression may be the predominant target of natural selection in humans and other species. Detecting selection acting on these elements is critical to understanding evolution but remains challenging because we do not know which mutations will affect gene regulation. RESULTS: To address this, we devise an approach to search for lineage-specific selection on three critical steps in transcriptional regulation: chromatin activity, transcription factor binding, and chromosomal looping. Applying this approach to lymphoblastoid cells from 831 individuals of either European or African descent, we find strong signals of differential chromatin activity linked to gene expression differences between ancestries in numerous contexts, but no evidence of functional differences in chromosomal looping. Moreover, we show that enhancers rather than promoters display the strongest signs of selection associated with sites of differential transcription factor binding. CONCLUSIONS: Overall, our study indicates that some cis-regulatory adaptation may be more easily detected at the level of chromatin than DNA sequence. This work provides a vast resource of genomic interaction data from diverse human populations and establishes a novel selection test that will benefit future study of regulatory evolution in humans and other species.

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PURPOSE OF REVIEW: Acute knee injuries are commonly encountered in both the clinical and sideline setting and may be treated operatively or non-operatively. This article describes an evidence-based approach to non-operative acute knee injury. This includes history, physical exam, imaging, and initial management. In addition, the non-operative management of three such injuries-ligament injury, meniscus injury, and patellar dislocation injury-will be discussed via a case-based practical approach. RECENT FINDINGS: Aside from grade III ACL tears, most acute knee ligament injuries, especially in the absence of other concurrent injuries, can be treated non-operatively. There is new evidence that acute traumatic meniscus tears in those younger than 40 can be successfully treated non-operatively and can do equally, as well as those that undergo surgery, at 1 year out from injury. Based on the current literature, a short period of knee bracing in extension with progression to weightbearing to tolerance is recommended after initial patellar dislocation. Many of the most common acute knee injuries, including MCL tears, meniscus tears, and patellar dislocations, can be managed non-operatively. A detailed systemic approach to initial evaluation, including pertinent history, physical exam, and appropriate imaging, is essential and complementary to the subsequent non-operative treatment algorithm.

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INTRODUCTION: On 22 November 2018, the French Society for Plastic, Reconstructive and Aesthetic Surgery recommended that Allergan® macrotextured breast implants be recalled, a decision endorsed by the French national health products safety agency (ANSM) on 2nd April 2019. At the Georges-François Leclerc Cancer Center (CGFL) in Dijon, we decided to stop using macrotextured implants as of November 2018 in favor of smooth implants. The purpose of this study is to evaluate the impact of the recall of macrotextured implants on breast reconstruction surgical practices and their complications. METHODS: This is a single-centre, retrospective study performed at the CGFL in Dijon, France. Reconstruction techniques and complications were compared between two periods, i.e. before the recall of macrotextured breast implants (period 1: 1st September 2017-November 22, 2018) and after the recall (period 2: 23 November 2018-31st March 2020). All patients who underwent breast reconstruction for the first time were included. RESULTS: Data were collected from 168 reconstructions in period 2, and 159 in period 2. The rate of use of breast implants during reconstructions decreased significantly in period 2 (53.6% vs. 23.9%; P<0.001). The rate of autologous reconstructions increased significantly for muscle sparing latissimus dorsi (2.4% vs. 12.6%; P<0.001) and exclusive fat grafting (9.5% vs. 21.5%; P<0.01). Clavien-Dindo Stage IIIb complications decreased in period 2 (10% vs. 18.4%; P=0.04). CONCLUSION: Since the recall of macrotextured breast implants, the reconstruction rate has decreased in our centre in favor of autologous techniques with lower complication rates.

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Acute myeloid leukemia (AML) is an aggressive hematologic malignancy requiring urgent treatment advancements. Ceramide is a cell-death-promoting signaling lipid that plays a central role in therapy-induced cell death. We previously determined that acid ceramidase (AC), a ceramide-depleting enzyme, is overexpressed in AML and promotes leukemic survival and drug resistance. The ceramidase inhibitor B-13 and next-generation lysosomal-localizing derivatives termed dimethylglycine (DMG)-B-13 prodrugs have been developed but remain untested in AML. Here, we report the in vitro anti-leukemic efficacy and mechanism of DMG-B-13 prodrug LCL-805 across AML cell lines and primary patient samples. LCL-805 inhibited AC enzymatic activity, increased total ceramides, and reduced sphingosine levels. A median EC50 value of 11.7 µM was achieved for LCL-805 in cell viability assays across 32 human AML cell lines. As a single agent tested across a panel of 71 primary AML patient samples, a median EC50 value of 15.8 µM was achieved. Exogenous ceramide supplementation with C6-ceramide nanoliposomes, which is entering phase I/II clinical trial for relapsed/refractory AML, significantly enhanced LCL-805 killing. Mechanistically, LCL-805 antagonized Akt signaling and led to iron-dependent cell death distinct from canonical ferroptosis. These findings elucidated key factors involved in LCL-805 cytotoxicity and demonstrated the potency of combining AC inhibition with exogenous ceramide.

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Bacterial adhesion is a fundamental process which enables colonisation of niche environments and is key for infection. However, in Legionella pneumophila, the causative agent of Legionnaires' disease, these processes are not well understood. The Legionella collagen-like protein (Lcl) is an extracellular peripheral membrane protein that recognises sulphated glycosaminoglycans (GAGs) on the surface of eukaryotic cells, but also stimulates bacterial aggregation in response to divalent cations. Here we report the crystal structure of the Lcl C-terminal domain (Lcl-CTD) and present a model for intact Lcl. Our data reveal that Lcl-CTD forms an unusual dynamic trimer arrangement with a positively charged external surface and a negatively charged solvent exposed internal cavity. Through Molecular Dynamics (MD) simulations, we show how the GAG chondroitin-4-sulphate associates with the Lcl-CTD surface via unique binding modes. Our findings show that Lcl homologs are present across both the Pseudomonadota and Fibrobacterota-Chlorobiota-Bacteroidota phyla and suggest that Lcl may represent a versatile carbohydrate binding mechanism.

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This cross-sectional study aimed at exploring the frequency and extent of knee joint lesions associated with delayed treatment of anterior cruciate ligament (ACL) injury. It enrolled 300 patients from 2020 to 2022 who were subjected to arthroscopy for anterior cruciate ligament reconstruction. The sample was comprised of Iraqi adult male patients from different regions of Iraq, and the surgical procedure was carried out in Al-Diwaniyah Teaching Hospital. The findings were recorded by Karl Storz's camera system. Dissection and arthroscopy were done under general anesthesia using an anterolateral portal technique. The study employed a visualization of the anterior cruciate ligament probing the meniscus and reaching the posteromedial space for the ramp lesion. The mean age of patients was 28.05±6.92 years, ranging from 19 to 35 years and the mean duration from onset of injury to the time of operation was 3.69±1.07 years, ranging from 6 months to 10 years. The arthroscopic examination revealed medial meniscus tear in 80% of the cases, lateral meniscus tear in 40% of the cases, cartilage lesion in 40% of the cases, and meniscus ramp lesions in 10% of the cases. Most cases of ACL tear are associated with a meniscus injury, cartilage defect, and collateral ligament tear. These serious lesions, such as complex meniscus tears or full articular cartilage defects, are a direct consequence of delayed treatment. Consequently, it is crucial to inform the patients about the significant issues that can arise due to treatment delays.

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Fractures around the elbow are often challenging to treat and in most cases require an extensive approach. Since the development of elbow arthroscopy, most authors have pointed out the potential advantages of a less invasive technique that can be useful for visualization and reduction of the articular fragments with an eventual percutaneous fixation. Arthroscopic techniques provide a limited exposure that may lead to a faster wound healing, lower rate of complications and thus, better recovery of range of motion. However, elbow arthroscopy is also a demanding technique, especially in a swollen and fractured joint, and it is not exempt of risks. The overall rate of complications has been rated from 1.5% to 11% and nerve injury rates from 1.26-7.5%.The objective of this review is to present the arthroscopic setup and general surgical technique for the management of elbow trauma and to define some clear indications. Patient positioning and operating room display is key in order to obtain success. In addition to the arthroscopic equipment, fluoroscopy is almost always necessary for percutaneous fixation and precise preparation is mandatory. In the last decade, literature regarding new portals or surgical tips for arthroscopic treatment of elbow fractures have been published.The main indications for fracture arthroscopic-assisted fixation are those articular fractures involving the coronoid, distal humerus shear fractures in the coronal plane (trochlear and capitellum fractures) and, more controversially, those affecting the radial head. The treatment of these type of fractures all arthroscopically is exponentially demanding as it might also require ligament repair. For coronoid fractures, it can be useful in Morrey type II and III, and O´Driscoll anteromedial facet fractures associated to a posteromedial instability pattern that also require a repair of the LCL. Although excellent results have been published, comparative series are scarce. Radial head fractures can also be approached arthroscopically in simple non-comminute fractures that can be fixed percutaneously.In conclusion, arthroscopy of the elbow is an excellent tool to better understand and visualize articular fractures of the elbow. However, despite the advances in surgical technique, whether it improves clinical and radiological results is still to be proven.

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INTRODUCTION: Acid ceramidase (hereafter referred as ASAH1) is an enzyme in sphingolipid metabolism that converts pro-survival ceramide into sphingosine. ASAH1 has been shown to be overexpressed in certain cancers. However, the role of ASAH1 in colorectal cancer still remain elusive. OBJECTIVE: The present study is aimed to understand how ASAH1 regulates colorectal cancer (CRC) progression and resistance to checkpoint inhibitor therapy. METHODS: Both pharmacological and genetic silencing of ASAH1 was used in the study. In vitro experiments were done on human and mouse CRC cell lines. The in vivo studies were conducted in NOD-SCID and BALB/c mice models. The combination of ASAH1 inhibitor and checkpoint inhibitor was tested using a syngeneic tumor model of CRC. Transcriptomic and metabolomic analyses were done to understand the effect of ASAH1 silencing. RESULTS: ASAH1 is overexpressed in human CRC cases, and silencing the expression resulted in the induction of immunological cell death (ICD) and mitochondrial stress. The ASAH1 inhibitor (LCL-521), either as monotherapy or in combination with an anti-PD-1 antibody, resulted in reduction of tumors and, through induction of type I and II interferon response, activation of M1 macrophages and T cells, leading to enhanced infiltration of cytotoxic T cells. Our findings supported that the combination of LCL-521 and ICIs, which enhances the antitumor responses, and ASAH1 can be a druggable target in CRC.

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Repair or reconstruction of the lateral collateral ligament (LCL) using autograft or allograft is a well-accepted treatment of posterolateral rotatory instability. The prevalence and causes for failure of LCL reconstruction are not well documented in the literature. Any approach to the assessment and management of failed LCL reconstruction must begin with understanding the risk factors for failure in the first place. Such understanding would likely make many failures preventable as well. In our experience, there are a number of identifiable preoperative risk factors concerning bony and/or soft tissue constraints for failure of LCL reconstruction. There are also operative factors such as tunnel and graft placement as well as excessive lateral condyle stripping that play a role in risk of failure. This report is an attempt to provide a systematic approach to identifying and managing the preoperative and operative risk factors. Further studies are warranted to determine the indications for, and success rates of surgical intervention in managing these risk factors.

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Purpose: The aim of this study was to evaluate the presence of residual instability in the knee after ACL reconstruction through the analysis of MRI findings. Methods: This study included patients who underwent isolated ACL reconstruction between December 2019 and December 2021, and had preoperative and postoperative MRI, clinical scores, and postoperative isokinetic measurements. The anterior tibial translation (ATT) distance, coronal lateral collateral ligament (LCL) sign, and femorotibial rotation (FTR) angle were compared preoperatively and postoperatively. The correlation between the changes in preoperative-postoperative measurements and postoperative measurements with clinical scores and isokinetic measurements was examined. The clinical outcomes were compared based on the presence of a postoperative coronal LCL sign. Inclusion criteria were set as follows: the time between the ACL rupture and surgery being 6 months, availability of preoperative and postoperative clinical scores, and objective determination of muscle strength using isokinetic dynamometer device measurements. Patients with a history of previous knee surgery, additional ligament injuries other than the ACL, evidence of osteoarthritis on direct radiographs, cartilage injuries lower limb deformities, and contralateral knee injuries were excluded from this study. Results: This study included 32 patients. After ACL reconstruction, there were no significant changes in the ATT distance (preoperatively: 6.5 ± 3.9 mm, postoperatively: 5.7 ± 3.2 mm) and FTR angle (preoperatively: 5.4° ± 2.9, postoperatively: 5.2° ± 3.5) compared to the preoperative measurements (p > 0.05). The clinical measurements were compared based on the presence of a postoperative coronal LCL sign (observed in 17 patients, not observed in 15 patients), and no significant differences were found for all parameters (p > 0.05). There were no observed correlations between postoperative FTR angle, postoperative ATT distance, FTR angle change, and ATT distance change values with postoperative clinical scores (p > 0.05). Significant correlations were observed between the high strength ratios generated at an angular velocity of 60° and a parameters FTR angle and ATT distance (p-values: 0.028, 0.019, and r-values: -0.389, -0.413, respectively). Conclusions: Despite undergoing ACL reconstruction, no significant changes were observed in the indirect MRI findings (ATT distance, coronal LCL sign, and FTR angle). These results suggest that postoperative residual tibiofemoral rotation and tibial anterior translation may persist; however, they do not seem to have a direct impact on clinical scores. Furthermore, the increase in tibial translation and rotation could potentially negatively affect the flexion torque compared to the extension torque in movements requiring high torque at low angular velocities.

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The conventional proportional-gain-feedback link can only obtain the smallest effective damping region (EDR) due to the control delay among all the active damping methods regarding the capacitor current feedback. The digitally controlled system tends to be unstable when the system resonant frequency reaches the critical frequency caused by the grid impedance variation. To weaken the adverse effect on the system caused by the control delay, phase-lead feedback links are applied along the feedback path to provide phase compensation. By taking the simplicity and reliability of the feedback links into account, this paper proposes an alternative to an ideal differentiator, which consists of the Tustin discrete form of 's' and a digital low-pass filter. This proposed method has an identical phase frequency characteristic as an ideal differentiator but a better magnitude frequency characteristic, and its EDR can reach [0, fs/3]. The system stability analysis is conducted under different resonant frequencies, and under the condition of a weak grid, the co-design approach of the active damper and digital controller is presented. Finally, the experimental results are shown to verify the proposed method.

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Background: The genesis of SMAC mimetic drugs is founded on the observation that many cancers amplify IAP proteins to facilitate their survival, and therefore removal of these pathways would re-sensitize the cells towards apoptosis. It has become increasingly clear that SMAC mimetics also interface with the immune system in a modulatory manner. Suppression of IAP function by SMAC mimetics activates the non-canonical NF-κB pathway which can augment T cell function, opening the possibility of using SMAC mimetics to enhance immunotherapeutics. Methods: We have investigated the SMAC mimetic LCL161, which promotes degradation of cIAP-1 and cIAP-2, as an agent for delivering transient costimulation to engineered BMCA-specific human TAC T cells. In doing so we also sought to understand the cellular and molecular effects of LCL161 on T cell biology. Results: LCL161 activated the non-canonical NF-κB pathway and enhanced antigen-driven TAC T cell proliferation and survival. Transcriptional profiling from TAC T cells treated with LCL161 revealed differential expression of costimulatory and apoptosis-related proteins, namely CD30 and FAIM3. We hypothesized that regulation of these genes by LCL161 may influence the drug's effects on T cells. We reversed the differential expression through genetic engineering and observed impaired costimulation by LCL161, particularly when CD30 was deleted. While LCL161 can provide a costimulatory signal to TAC T cells following exposure to isolated antigen, we did not observe a similar pattern when TAC T cells were stimulated with myeloma cells expressing the target antigen. We questioned whether FasL expression by myeloma cells may antagonize the costimulatory effects of LCL161. Fas-KO TAC T cells displayed superior expansion following antigen stimulation in the presence of LCL161, suggesting a role for Fas-related T cell death in limiting the magnitude of the T cell response to antigen in the presence of LCL161. Conclusions: Our results demonstrate that LCL161 provides costimulation to TAC T cells exposed to antigen alone, however LCL161 did not enhance TAC T cell anti-tumor function when challenged with myeloma cells and may be limited due to sensitization of T cells towards Fas-mediated apoptosis.

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Background: Varus posteromedial rotatory instability is a relatively rare elbow injury, that has been infrequently reported in published literature. We intended to evaluate the outcomes of surgical management of this rare injury with anteromedial coronoid fixation, and, in selected patients, lateral ulnar collateral ligament (LUCL) repair. Methods: Between 2017 and 2020, we identified 12 patients with anteromedial coronoid fractures, and a varus posteromedial rotatory instability, who underwent surgery for fixation of the coronoid fracture, with or without LCL repair. All the included patients were either O'Driscoll subtype 2-2, or subtype 2-3. All the 12 patients were followed up for a minimum of 24 months, and their functional outcomes assessed using the Mayo Elbow Performance Score (MEPS). Results: The mean MEPS recorded in our study was 92.08, and the mean range of elbow flexion achieved was 124.2°. The mean flexion contracture in our patients was 5.83°. Three of our twelve patients (25%) suffered from elbow stiffness even at final follow-up. The results were graded as Excellent in eight, Good in three, and Fair in one patient. Conclusion: Coronoid fractures and LUCL disruptions associated with varus posteromedial rotatory instability can be reliably managed by employing a protocol that combines radiographic parameters, as well as intra-operative assessments of stability. While surgical intervention successfully restored stability, there is a learning curve to the management of these injuries and complications are not uncommon, particularly elbow stiffness. Hence, in addition to surgical fixation, emphasis should also be placed on intensive post-operative rehabilitation to improve outcomes.