Publisher Correction: Recycling lithium-ion batteries from electric vehicles.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Recycling lithium-ion batteries from electric vehicles.

Rapid growth in the market for electric vehicles is imperative, to meet global targets for reducing greenhouse gas emissions, to improve air quality in urban centres and to meet the needs of consumers, with whom electric vehicles are increasingly popular. However, growing numbers of electric vehicles present a serious waste-management challenge for recyclers at end-of-life. Nevertheless, spent batteries may also present an opportunity as manufacturers require access to strategic elements and critical materials for key components in electric-vehicle manufacture: recycled lithium-ion batteries from electric vehicles could provide a valuable secondary source of materials. Here we outline and evaluate the current range of approaches to electric-vehicle lithium-ion battery recycling and re-use, and highlight areas for future progress.

Statistical Morphology and Fragment Mapping of Complex Proximal Humeral Fractures.

Background and Objectives: Proximal humerus fractures (PHFs) are common in the elderly, but the treatment results are often poor. A clear understanding of fracture morphology and distribution of cortical bone loss is important for improved surgical decision making, operative considerations, and new implant designs. The aim of this study was to develop a 3D segmentation fracture mapping technique to create a statistical description of the spatial pattern and cortical bone loss of complex PHFs. Materials and Methods: Fifty clinical computed tomography (CT) scans of complex PHFs and their contralateral intact shoulders were collected. In-house software was developed for semi-automated segmentation and fracture line detection and was combined with manual fracture reduction to the contralateral template in a commercial software. A statistical mean model of these cases was built and used to describe probability maps of the fracture lines and cortical fragments. Results: The fracture lines predominantly passed through the surgical neck and between the tuberosities and tendon insertions. The superior aspects of the tuberosities were constant fragments where comminution was less likely. Some fracture lines passed through the bicipital sulcus, but predominantly at its edges and curving around the tuberosities proximally and distally. Conclusions: A comprehensive and systematic approach was developed for processing clinical CT images of complex fractures into fracture morphology and fragment probability maps and applied on PHFs. This information creates an important basis for better understanding of fracture morphology that could be utilized in future studies for surgical training and implant design.

The anatomy and variation of the coracoid attachment of the subclavius muscle in humans.

The functions of the subclavius muscle (SM) are described as stabilization of the sternoclavicular joint (SCJ) and resisting elevation of the lateral end of the clavicle. During systematic cadaveric dissections, we observed additional fibrous structures, previously described as variants of the anatomy, extending from the SM and inserting into the coracoid process (CP). Due to the high incidence of these structures in our dissections, we hypothesized that the attachment at the CP is more common than appreciated and that, as a corollary, the function of the SM was (or has been) more complex than simply depressing the clavicle and generating stability at the SCJ. For our investigation, fifty-two upper extremities of 26 human cadavers were dissected. The SM was demonstrated from costal to clavicular attachment. We documented additional fibrous structures apparently derived from the SM inserting into the CP. Measurements of the length of the SM, the length of its attachment, and the length of the clavicle were taken in situ, with the specimens supine and the upper extremity in the anatomical position. Variations in the anatomy of the SM and its coracoidal attachment were recorded, and potential correlations were investigated. For documentation purposes photographs and video sequences of passive motion of the shoulder girdle of the specimens were taken. In 49 of the 52 specimens we found additional fibrous structures passing from the SM to the CP. We differentiated three types: (1) a strong cord-like structure; (2) a small or thin cord-like structure or structures; and (3) a planar twisted sheet-like structure. The SM and its extension to the CP appears to contribute to a 'functional scapular suspension system' together with the other muscles enveloped by the clavipectoral fascia (pectoralis minor, coracobrachialis and the short head of the biceps brachii). This system assists in the control of the position of the scapula in relation to the thorax, particularly in elevated positions of the upper extremity. We speculate that the differentiation of the fibrous structure depends on the functional demands of the individual. Level of Evidence: Basic science study.

Specific Binding of Primary Ammoniums in Aqueous Media by Homooxacalixarenes Incorporated into Micelles.

The development of artificial receptors for efficient recognition of analytes in water is a challenging task. Homooxacalix[3]arene-based receptor 1, which is selective toward primary ammoniums in organic solvents, was transferred into water following two different strategies: direct solubilization and micellar incorporation. Extensive 1H NMR studies showed that recognition of ammoniums is only observed in the case of micellar incorporation, highlighting the beneficial effect of the microenvironment of the micellar core. The selectivity of the system for primary ammoniums over secondary and tertiary ones was also maintained. The hydrophobic effect plays an important role in the recognition properties, which are counterion-dependent due to the energy penalty for the dissociation of certain ammonium salts in the apolar micellar core. This study shows that the straightforward self-assembly process used for the encapsulation of artificial receptors in micelles is an efficient strategy for developing water-soluble nanosized supramolecular recognition systems.

Surgical treatment, complications, reoperations, and healthcare costs among patients with clavicle fracture in England.

INTRODUCTION: The clinical and economic burden of clavicle fractures in England is not well documented. This study evaluated rates of surgical treatment, post-surgical complications, reoperations and costs in patients with clavicle fractures using the Clinical Practice Research Datalink (CPRD) database. METHODS: CPRD data were linked to National Health Service Hospital Episode Statistics data. Patients with a diagnosis of clavicle fracture between 2010-2018 were selected in CPRD (date of fracture = index date). Of those, patients with surgical intervention within 180 days from index fracture were identified. Rates of post-surgical complications (i.e., infection, non-union, and mal-union), reoperations (for device removal or for postoperative complications), post-operative costs and median time to reoperations were evaluated up to 2 years after surgery. RESULTS: 21,340 patients with clavicle fractures were identified (mean age 35.0 years(standard deviation (SD): 26.5), 66.7% male). Surgery was performed on 672 patients (3.2% of total cohort) at an average 17.1 (SD: 25.2) days post-fracture. Complications (i.e., infection, non-union, or malunion) affected 8.1% of surgically treated clavicle fracture patients; the rate of infection was 3.5% (95% CI, 1.7%- 5.2%), non-union 4.4% (95% CI, 2.4%-6.5%), and mal-union 0.3% (95% CI, 0%-0.7%). Adjusting for age, gender, comorbidities and time to surgery, the all-cause reoperation rate was 20.2% (13.2%-30.0%) and the adjusted rate of reoperation for implant removal was 17.0% (10.7%-25.9%)-84% of all-cause reoperations were thus performed for implant removal. Median time to implant removal was 254 days. The mean cost of reoperations for all causes was £5,000. The most expensive reoperations were for cases that involved infection (mean £6,156). CONCLUSIONS: Complication rates following surgical clavicle fracture care averaged 8.1%. However, reoperation rates exceed 20%, the vast majority of reoperations being performed for device removal. Technologies to alleviate secondary device removal surgeries would address a significant clinical unmet need.

Numerical simulation of wave propagation through interfaces using the extended finite element method for magnetic resonance elastography.

Magnetic resonance elastography (MRE) is an elasticity imaging technique for quantitatively assessing the stiffness of human tissues. In MRE, finite element method (FEM) is widely used for modeling wave propagation and stiffness reconstruction. However, in front of inclusions with complex interfaces, FEM can become burdensome in terms of the model partition and computationally expensive. In this work, we implement a formulation of FEM, known as the eXtended finite element method (XFEM), which is a method used for modeling discontinuity like crack and heterogeneity. Using a level-set method, it makes the interface independent of the mesh, thus relieving the meshing efforts. We investigate this method in two studies: wave propagation across an oblique linear interface and stiffness reconstruction of a random-shape inclusion. In the first study, numerical results by XFEM and FEM models revealing the wave conversion rules at linear interface are presented and successfully compared to the theoretical predictions. The second study, investigated in a pseudo-practical application, demonstrates further the applicability of XFEM in MRE and the convenience, accuracy, and speed of XFEM with respect to FEM. XFEM can be regarded as a promising alternative to FEM for inclusion modeling in MRE.

Ensuring Equity and Inclusion in Virtual Care Best Practices for Diverse Populations of Youth with Chronic Pain.

Poor access to care is a top patient-oriented research priority for youth with chronic pain in Canada, and the COVID-19 pandemic has exacerbated these concerns. Our patient-oriented project team engaged with marginalized and racialized youth with chronic pain (Black youth with sickle cell disease, Indigenous youth and youth with complex medical needs) and their families to ensure that best practice recommendations for virtual care are inclusive and equitable. Input provided through virtual round-table discussions improved recommendations for leveraging, implementing and selecting best platforms for virtual care for youth with chronic pain and identified new gaps for future research, practice and policy change.

Core set of unfavorable events of proximal humerus fracture treatment defined by an international Delphi consensus process.

BACKGROUND: Proximal humerus fracture (PHF) complications, whether following surgery or nonoperative management, require standardization of definitions and documentation for consistent reporting. We aimed to define an international consensus core event set (CES) of clinically-relevant unfavorable events of PHF to be documented in clinical routine practice and research. METHODS: A Delphi exercise was implemented with an international panel of experienced shoulder trauma surgeons selected by survey invitation of AO Trauma members. An organized list of PHF events after nonoperative or operative management was developed and reviewed by panel members using on-line surveys. The proposed core set was revised regarding event groups along with definitions, specifications and timing of occurrence. Consensus was reached with at least a two-third agreement. RESULTS: The PHF consensus panel was composed of 231 clinicians worldwide who responded to at least one of two completed surveys. There was 93% final agreement about three intraoperative local event groups (device, osteochondral, soft tissue). Postoperative or nonoperative event terms and definitions organized into eight groups (device, osteochondral, shoulder instability, fracture-related infection, peripheral neurological, vascular, superficial soft tissue, deep soft tissue) were approved with 96 to 98% agreement. The time period for documentation ranged from 30 days to 24 months after PHF treatment depending on the event group and specification. The resulting consensus was presented on a paper-based PHF CES documentation form. CONCLUSIONS: International consensus was achieved on a core set of local unfavorable events of PHF to foster standardization of complication reporting in clinical research and register documentation. TRIAL REGISTRATION: Not applicable.

The apparent mechanical effect of isolated amyloid-ß and α-synuclein aggregates revealed by multi-frequency MRE.

Several biological processes are involved in dementia, and fibrillar aggregation of misshaped endogenous proteins appears to be an early hallmark of neurodegenerative disease. A recently developed means of studying neurodegenerative diseases is magnetic resonance elastography (MRE), an imaging technique investigating the mechanical properties of tissues. Although mechanical changes associated with these diseases have been detected, the specific signal of fibrils has not yet been isolated in clinical or preclinical studies. The current study aims to exploit the fractal-like properties of fibrils to separate them from nonaggregated proteins using a multi-frequency MRE power law exponent in a phantom study. Two types of fibril, α-synuclein (α-Syn) and amyloid-ß (Aß), and a nonaggregated protein, bovine serum albumin, used as control, were incorporated in a dedicated nondispersive agarose phantom. Elastography was performed at multiple frequencies between 400 and 1200 Hz. After 3D-direct inversion, storage modulus (G'), phase angle (ϕ), wave speed and the power law exponent (y) were computed. No significant changes in G' and ϕ were detected. Both α-Syn and Aß inclusions showed significantly higher y values than control inclusions (P = 0.005) but did not differ between each other. The current phantom study highlighted a specific biomechanical effect of α-Syn and Aß aggregates, which was better captured with the power law exponent derived from multi-frequency MRE than with single frequency-derived parameters.

Comparison of pulsed and oscillating gradient diffusion-weighted MRI for characterizing hepatocellular nodules in liver cirrhosis: ex vivo study in a rat model.

BACKGROUND: In contrast to classical pulsed gradient diffusion-weighted MRI, oscillating gradient diffusion-weighted MR imaging (DWI) is sensitive to short distance diffusion changes at the intracellular level. PURPOSE: To compare the diagnostic performance of pulsed and oscillating DWI for characterizing hepatocellular nodules in a rat model of hepatic cirrhosis. STUDY TYPE: Prospective, experimental study. ANIMAL MODEL: Cirrhosis was induced by weekly intraperitoneal injection of diethylnitrosamine in Wistar rats. FIELD STRENGTH/SEQUENCE: Ex vivo liver MRI was performed at 7T with T1 -weighted, T2 -weighted, pulsed, and oscillating gradient diffusion-weighted sequences. ASSESSMENT: Apparent diffusion coefficient from pulsed (ADCpulsed ) and oscillating gradient (ADCoscillating ) sequences was calculated in 82 nodules identified on the T1 /T2 -weighted images and on pathological examination. Two pathologists classified the nodules in three categories: benign (regenerative and low-grade dysplastic nodules), with intermediate malignancy (high-grade dysplastic nodules and early hepatocellular carcinomas) and overtly malignant (progressed hepatocellular carcinomas). STATISTICAL TESTS: Differences between groups were assessed with Kruskal-Wallis and Mann-Whitney tests. RESULTS: ADC, mainly ADCoscillating , increased in the group of nodules with intermediate malignancy (ADCpulsed : 0.75 ± 0.25 × 10-3 mm2 /s vs. 0.64 ± 0.07 × 10-3 mm2 /s in benign nodules, P = 0.025; ADCoscillating : 0.81 ± 0.20 × 10-3 mm2 /s vs. 0.65 ± 0.13 × 10-3 mm2 /s, P = 0.0008) and ADCpulsed decreased in the group of progressed hepatocellular carcinomas (ADCpulsed : 0.60 ± 0.08 × 10-3 mm2 /s, P = 0.042; ADCoscillating : 0.68 ± 0.08 × 10-3 mm2 /s, P = 0.1). DATA CONCLUSION: ADC during hepatocarcinogenesis in rats increased in nodules with intermediate malignancy and decreased in progressed hepatocellular carcinomas. Our results suggest that oscillating gradient DWI is more sensitive to the early steps of hepatocarcinogenesis and might be useful for differentiating between high-grade dysplastic nodules / early hepatocellular carcinomas and regenerating nodules / low-grade dysplastic nodules. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:1065-1074.

Specific Binding of Primary Ammonium Ions and Lysine-Containing Peptides in Protic Solvents by Hexahomotrioxacalix[3]arenes.

The binding of ammonium ions by two homooxacalix[3]arene-based receptors was studied using NMR spectroscopy and in silico methods. Both receptors are shown to endocomplex, even in a protic environment, a large variety of primary ammonium ions, including biomolecules. The binding mode is similar for all guests with the ammonium ion deeply inserted into the polyaromatic cavity and its NH3+ head nearly in the plane defined by the three oxygen atoms of the 18-crown-3 moiety, thus enabling it to establish three H-bonds with the ethereal macrocycle. The remarkable electronic, size, and shape complementarity between primary ammonium ions and the two cavity-based receptors leads to an unprecedented specificity for primary ammonium ions over secondary, tertiary, and quaternary ones. These binding properties were exploited for the selective liquid-liquid extraction of primary ammonium salts from water and for the selective recognition of lysine-containing peptides, opening new perspectives in the field of peptide sensing.

In vitro distinction between proinflammatory and antiinflammatory macrophages with gadolinium-liposomes and ultrasmall superparamagnetic iron oxide particles at 3.0T.

BACKGROUND: Inflammation involves a heterogeneous macrophage population, for which there is no readily available MR assessment method. PURPOSE: To assess the feasibility of distinguishing proinflammatory M1 and antiinflammatory M2 macrophages at MRI enhanced with gadolinium liposomes or ultrasmall superparamagnetic iron oxide particles. STUDY TYPE: In vitro. SPECIMEN: We employed cultured RAW macrophages. M0 macrophages were polarized with lipopolysaccharide (LPS) or interleukin-4 (IL-4), resulting in M1 or M2 macrophages. The macrophages were incubated with gadolinium (±rhodamine) liposomes or iron oxide particles and cell pellets were prepared for MRI. FIELD STRENGTH/SEQUENCE: Transverse relaxation rates and quantitative susceptibility were obtained at 3.0T with multiecho turbo spin echo and spoiled gradient echo sequences. ASSESSMENT: MRI results were compared with confocal microscopy, flow cytometry, and expression of endocytosis, M1 and M2 genes. STATISTICAL TESTS: Mann-Whitney and Kruskal-Wallis tests were performed. RESULTS: Higher transverse relaxation rates and susceptibility were observed in M1 than in M2 and M0 macrophages (P < 0.01 both with liposomes and USPIO) and significantly different susceptibility in M2 and M0 macrophages (P < 0.01 both with liposomes and USPIO). These MRI results were confirmed at confocal microscopy and flow cytometry. LPS macrophages displayed M1 gene expression, whereas IL-4 macrophages showed M2 polarization and lower endocytosis gene expression rates. DATA CONCLUSION: These in vitro results show that it is feasible to distinguish between proinflammatory M1 and antiinflammatory M2 macrophages according to their level of contrast agent uptake at MRI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:1166-1173.

Renal parenchyma impairment characterization in partial unilateral ureteral obstruction in mice with intravoxel incoherent motion-MRI.

Ureteropelvic junction obstruction constitutes a major cause of progressive pediatric renal disease. The biological mechanisms underlying the renal response to obstruction can be investigated using a clinically relevant mouse model of partial unilateral ureteral obstruction (pUUO). Renal function and kidney morphology data can be evaluated using renal ultrasound, scintigraphy and uro-magnetic resonance imaging (uro-MRI), but these methods are poorly linked to histological change and not all are quantitative. Here, we propose to investigate pUUO for the first time using an intravoxel incoherent motion diffusion sequence. The aim of this study was to quantitatively characterize impairment of the kidney parenchyma in the pUUO model. This quantitative MRI method was able to assess the perfusion and microstructure of the kidney without requiring the injection of a contrast agent. The results suggest that a perfusion fraction (f) reduction is associated with a decrease in the volume of the renal parenchyma, which could be related to decreased renal vascularization. The latter may occur before impairment by fibrosis and the findings are in accordance with the literature using the UUO mice model and, more specifically, on pUUO. Further investigation is required before this technique can be made available for the diagnosis and management of children with antenatal hydronephrosis and to select the optimal timing of surgery if required.

Rheological determinants for simultaneous staging of hepatic fibrosis and inflammation in patients with chronic liver disease.

The purpose of this study is to investigate the use of fundamental rheological parameters as quantified by MR elastography (MRE) to measure liver fibrosis and inflammation simultaneously in humans. MRE was performed on 45 patients at 3 T using a vibration frequency of 56 Hz. Fibrosis and inflammation scores were obtained from liver biopsies. Biomechanical properties were quantified in terms of complex shear modulus G* as well as shear wave phase velocity c and shear wave attenuation α. A rheological fractional derivative order model was used to investigate the linear dependence of the free model parameters (dispersion slope y, intrinsic speed c0 , and intrinsic relaxation time τ) on histopathology. Leave-one-out cross-validation was then utilized to demonstrate the effectiveness of the model. The intrinsic speed c0 increases with hepatic fibrosis, while an increased relaxation time τ is reflective of more inflammation of the liver parenchyma. The dispersion slope y does not depend either on fibrosis or on inflammation. The proposed rheological model, given this specific parameterization, establishes the functional dependences of biomechanical parameters on histological fibrosis and inflammation. The leave-one-out cross-validation demonstrates that the model allows identification, from the MRE measurements, of the histology scores when grouped into low-/high-grade fibrosis and low-/high-grade inflammation with significance levels of P = 0.0004 (fibrosis) and P = 0.035 (inflammation). The functional dependences of intrinsic speed and relaxation time on fibrosis and inflammation, respectively, shed new light onto the impact hepatic pathological changes on liver tissue biomechanics in humans. The dispersion slope y appears to represent a structural parameter of liver parenchyma not impacted by the severity of fibrosis/inflammation present in this patient cohort. This specific parametrization of the well-established rheological fractional order model is valuable for the clinical assessment of both fibrosis and inflammation scores, going beyond the capability of the plain shear modulus measurement commonly used for MRE.

The congenital undescended scapula syndrome: Sprengel and the cleithrum: a case series and hypothesis.

BACKGROUND: Sprengel deformity is a rare congenital shoulder girdle anomaly characterized by scapula malposition, periscapular muscle atrophy, and limited shoulder movement. Traditionally, it has been managed by omovertebral bar excision and muscle transplantation procedures guided by age and Cavendish grade. We present a unique observation in humans: a case series with Sprengel deformity possessing a cleithrum, an ancestral remnant of shoulder girdle development found in archaic bony fish. METHODS: Nine patients presented with so-called Sprengel deformity to a tertiary referral shoulder clinic. All were assessed clinically and radiologically with scapular radiographs and computed tomography or magnetic resonance imaging scans. The clinical and radiologic features were classified according to Cavendish and Rigault systems, respectively, and the scapular ratio was assessed. RESULTS: All patients were assigned grade 4 on the Cavendish scale. Six were grade 2 and 3 were grade 3 on the Rigault scale. The distinguishing pathoanatomic feature was partial endomuscular ossification of medial scapular suspension muscles, analogous to the cleithrum of bony fish. Five cases were treated operatively and 4 nonoperatively. Mean elevation and abduction significantly improved in surgical cases. DISCUSSION AND CONCLUSION: This finding not only challenges classic management of these rare patients but offers insight into scapular embryology and development. The association of scapular developmental and urogenital anomalies suggests that screening of the renal tract and genetic investigation in those with undescended scapula syndrome be considered. We suggest, to emphasize the nature of incomplete scapular descent and associated congenital anomalies and to clarify imprecise common use of the term Sprengel deformity, that this condition be called the congenital undescended scapula syndrome.

The management of infected elbow arthroplasty by two-stage revision.

BACKGROUND: Deep prosthetic infection is a potentially devastating complication after total elbow arthroplasty, with an incidence of up to 12%. This study examined the demographics, microbiologic profile, and outcomes of infected total elbow arthroplasty treated with 2-stage revision in a tertiary referral unit. METHODS: We identified 19 consecutive patients (mean age, 65 years) undergoing revision arthroplasty for deep prosthetic infection. All patients underwent a first-stage procedure with removal of implants, débridement, and insertion of an antibiotic-loaded cement spacer, followed by at least 6 weeks of intravenous antibiotics. Fourteen patients required a second-stage revision. RESULTS: Five patients did not undergo a second-stage procedure because of patient choice (n = 2), medical or surgical risk factors (n = 2), and death from an unrelated cause (n = 1). Of the 19 patients undergoing a first-stage procedure, 16 (84%) remained infection free, and 11 of the 14 patients (79%) undergoing reimplantation of an elbow prosthesis remained infection free. Six patients required further surgery (3 for recurrent infection, 3 for noninfective indications). The commonest infecting organism was Staphylococcus aureus (47%). A degree of postoperative ulnar nerve dysfunction occurred in 37% of patients, but all resolved fully without further treatment. CONCLUSIONS: Management of prosthetic joint infection using 2-stage revision can result in high rates of eradication, although rates of reoperation and transient ulnar nerve dysfunction are high.

Teres major muscle - insertion footprint.

Teres major muscle (TM) and latissimus dorsi muscle (LD) are frequently used in muscle transfers around the shoulder girdle. Some authors have suggested harvesting techniques in which the muscle is detached in continuity with a bone segment. Information on the bony attachment footprint of these muscles is lacking. The purpose of this study was to investigate the region of attachment of the TM to facilitate safe and complete harvesting with a bone segment where it is indicated, and to determine the relationship of the TM footprint with that of the LD. Twenty-eight upper extremities of 14 human cadavers (six female, eight male) were investigated during the students' dissection course in the winter term 2012. The attachment footprints were photographed and the images were processed with ImageJ Version 1.46r. The TM attachment footprint at the crest of the lesser tubercle had an average dimension of 187 ±â€…89 mm2 . It was 49.6 ±â€…7.9 mm long and 7.4 ±â€…2.5 mm wide. The bony attachment of the LD within the bicipital groove, just below the tendon of the long head of the biceps muscle, had an area of 94 ±â€…37 mm2 . It was 36.5 ±â€…8 mm long and 3.7 ±â€…1.2 mm wide. Both muscles were separated by 4.4 ±â€…1.7 mm and their attachments overlapped in the craniocaudal direction by 24.4 ±â€…12.4 mm. Earlier studies have investigated the dimensions of the muscles' tendons close to the attachment not the bony attachment itself. The dimension of the attachment of the TM was larger than that of the LD. The ratio between the footprint areas was approximately 2:1. This information should be considered by surgeons undertaking transfers, which include a bony segment of the muscle insertion.

Strong antineoplastic effects of metformin in preclinical models of liver carcinogenesis.

Studies suggest that metformin, widely used for treating Type 2 diabetes, possesses innate antineoplastic properties. For metabolic syndrome patients with hepatocellular carcinoma (HCC), metformin may provide antitumoral effects. We evaluated the impact of metformin on tumour growth and visceral fat composition using relevant preclinical models of metabolic syndrome. Studies were performed in three hepatoma cell lines, in HepG2 xenograft mice fed with standard chow (SC) diet, 60% high-fat diet (HFD) or 30% fructose diet (FR), and an ex vivo model of human cultured HCC slices. Visceral fatty acid composition was analysed by magnetic resonance imaging (MRI). Metformin had a dose-dependent inhibitory effect on cell proliferation and apoptosis in vitro through the deregulation of mTOR/AMPK, AKT and extracellular signal regulated kinase (ERK) signalling pathways. Tumour engraftment rates were higher in HFD mice than SC mice (hepatic: 79% compared with 25%, P=0.02) and FR mice (subcutaneous: 86% compared with 50%, P=0.04). Subcutaneous tumour volume was increased in HFD mice (+64% compared with FR and SC, P=0.03). Metformin significantly decreased subcutaneous tumour growth via cell-cycle block and mammalian target of rapamycin (mTOR) pathway inhibition, and also induced hypoxia and decreased angiogenesis. In ex vivo tumour slices, metformin treatment led to increased necrosis, decreased cyclin D1 and increased carbonic anhydrase-9 (CA-9). Metformin caused qualitative changes in visceral fat composition of HFD mice, with decreased proportions of polyunsaturated fatty acids (14.6% ± 2.3% compared with 17.9% ± 3.0%, P=0.04). The potent antitumoral effects of metformin in multiple preclinical models implicating several molecular mechanisms provide a strong rationale for clinical trials including combination studies in HCC patients.

Posterior shoulder dislocation with associated reverse Hill-Sachs lesion: treatment options and functional outcome after a 5-year follow up.

BACKGROUND: The current study describes several surgical techniques for the treatment of the reverse Hill - Sachs lesion after posterior shoulder dislocation; we also aimed to present long term results followed for a minimum of five years. METHODS: This study is a prospective case series of 17 patients who were treated in our clinic between 2008 and 2011. Patients with a defect size smaller than 25% of the articular surface were treated conservatively. An endoprosthesis of the glenohumeral joint was implanted in patients with a defect size bigger than 40%. All remaining patients were treated by a variety of operative techniques, depending on the quality of the bone and size of the defect. RESULTS: Twelve of seventeen patients had a defect size of the humeral articular surface between 25% and 40% with a mean age of 39 years. Depending on the defect size these patients were treated with retrograde chondral elevation, antegrade cylindrical graft or a graft of the iliac bone crest with an open approach. All the procedures showed fair results, e.g. the open approach with a graft of the iliac bone crest (2010: Dash 3.89, Constant 90.33, Rowe 86.67; 2015: Dash 2.22, Constant 92.00, Rowe 93.33). CONCLUSION: The open approach is not a disadvantage for the functional outcome. The treatment algorithm should involve the superficial size of the defect as well as the depth of the defect and the time interval between the dislocation and the surgical treatment. TRIAL REGISTRATION: 223/2012BO2 , 02 August 2010.