Different approach to charcot neuroarthropathy: A case report.

INTRODUCTION AND IMPORTANCE: Charcot neuroarthropathy (CN) is a degenerative, progressive disease affecting the ankle and foot and it is usually a disabling factor in diabetic patients. Surgical management of CN aims to obtain a painless stable plantigrade foot which can be achieved through fusion. Achieving joint arthrodesis in CN usually carries a high failure rate. CASES PRESENTATION: We presented two patients with late-stage CN foot deformity. The first case is a 52-year-old female with CN on her left ankle and presented without any infection or prior correction. The second case reported a 47-year-old man with complaints of deformity on his right ankle, he had undergone surgical treatment with an external fixator before, and now presented with infection in the surgical site. CLINICAL DISCUSSION: Ankle arthrodesis has been considered by many as the treatment of choice for severe and late-stage CN foot. This treatment aims to give a rigid enough fixation which will maintain the stability of the ankle joint and prevents further destruction of surrounding tissue. Multiple modalities of treatment are available and must be chosen accordingly to each clinical case. Minimal implants and the use of multiple bone grafts could be considered as a plan of treatment. Both patients have promising and positive results from the two procedures. CONCLUSION: Treatment of CN Foot with internal plate fixation combined with fibular strut graft seemed to give promising results, both radiographically and functionally. Furthermore, a slight modification of treatment with a minimal implant or iliac graft may be considered.

Psychological Distress Amongst Medical Laboratory Professionals Involved in COVID-19-Related Duties: A Nationally Stratified Cross-Sectional Survey, Ghana.

To assess the prevalence and factors associated with psychological distress (PD) and Medical Laboratory Professionals (MLPs) involvement in COVID-19-related duties. This study adopted an online cross-sectional, nationally stratified survey among 473 MLPs using Google Form with a designated link; Depression, anxiety, and stress scale-21 (DASS-21) was used to measure depression, anxiety, and stress (secondary outcome). We employed generalized Negative Binomial (NBR) and Poisson regression analytical approach to our study outcomes. All analyses were performed using Stata 16, and P-value≤.05 deemed significant. The overall DASS-21 score ranged from asymptomatic psychological distress to severe symptomatic PD. The prevalence of depression, anxiety, and stress were 9.1 [95%CI=6.8-12.0], 17.8 [95%CI=14.6-21.5], and 7.5 [95%CI=5.4-10.1], respectively. The result evinced a high and significant association; the univariate NBR predicted a significant increase of PD score by 12% and 18% among participants who were involved in one and two or more COVID-19-related duties, respectively, (ß[95%CI] = .12 [.05-.18] and .18 [.10-.26], respectively). A binary outcome predicted approximately 2-folds of overall psychological distress among participants involved in two or more COVID-19-related duties compared with non-involvement (adjusted Prevalence Ratio [95%CI]= 2.34 [1.12-4.85]). For depression, anxiety, and stress symptoms, both univariate and multivariate data analyses evinced a higher disadvantage among MLP involved in COVID-19-related duties. We observed a high tendency of experiencing significant psychological distress amongst MLP involved in COVID-19-related duties. Experience of psychological distress increased with deeper involvement in COVID-19-related activities. Psychological support should be extended to MLPs to limit the effect of these negative emotions on their cognitive and social behavior as well as job performance.

Mesenchymal stem cell secretome decreases the inflammatory response in annulus fibrosus organ cultures.

Mesenchymal stem/stromal cell (MSC)-based therapies have been proposed for back pain and disc degeneration, despite limited knowledge on their mechanism of action. The impact of MSCs/their secretome on annulus fibrosus (AF) cells and tissue was analysed in bovine AF organ cultures (AF-OCs) exposed to upper-physiological cyclic tensile strain (CTS, 9 %, 1 Hz, 3 h/d) and interleukin (IL)-1ß in a custom-made device. A 4 d treatment of the CTS + IL-1ß-stimulated AF-OCs with MSC secretome downregulated the expression of inflammation markers [IL-6, IL-8, prostaglandin-endoperoxide synthase 2 (PTGS2)], complement system regulators [cluster of differentiation (CD)46, CD55, CD59] and matrix metalloproteinase 1 but also of tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and collagen type I. At the protein level, it was confirmed that IL-6, MMP-3 and collagen content was decreased in AF-OCs treated with the MSC secretome compared to the CTS + IL-1ß stimulation alone. 9 d after treatment, a biomechanical peel-force test showed that the annular adhesive strength was significantly decreased by the MSC secretome treatment. Overall, MSC secretome had a stronger impact on AF tissue than MSCs in co-culture. The secretome contributed to a decrease in the inflammatory and catabolic status of AF cells activated by CTS + IL-1ß and played a role in the regulation of the complement system. However, it also contributed to a decrease in collagen at the gene/protein level and in AF mechanical strength compared to the CTS + IL-1ß stimulation alone. Therefore, the use of MSC secretome requires further investigation regarding its influence on disc matrix properties.

Animal models for studying metaphyseal bone fracture healing.

An estimated 2 million osteoporotic fractures occur annually in the US, resulting in a dramatic reduction in quality of life for affected patients and a high economic burden for society. Osteoporotic fractures are frequently located in metaphyseal bone regions. They are often associated with healing complications, because of the reduced healing capacity of the diseased bone tissue, the poor primary stability of the fracture fixation in the fragile bone, and the high frequency of comorbidities in these patients. Therefore, osteoporotic fractures require optimised treatment strategies to ensure proper bone healing. Preclinical animal models can help understanding of the underlying mechanisms and development of new therapies. However, whereas diaphyseal fracture models are widely available, appropriate animal models for metaphyseal fracture healing are scarce, although essential for translational research. This review covers large and small animal models for metaphyseal fracture healing. General requirements for suitable animal models are presented, as well as advantages and disadvantages of the current models. Furthermore, differences and similarities between metaphyseal and diaphyseal bone fracture healing are discussed. Both large- and small-animal models are available for studying metaphyseal fracture healing, which mainly differ in fracture location and geometry as well as stabilisation techniques. Most common used fracture sites are distal femur and proximal tibia. Each model found in the literature has certain advantages and disadvantages; however, many lack standardisation resulting in a high variability or poor mimicking of the clinical situation. Therefore, further refinement ofanimal models is needed especially to study osteoporotic metaphyseal fracture healing.

Degeneration alters the biomechanical properties and structural composition of lateral human menisci.

OBJECTIVE: Because the literature relating to the influence of degeneration on the viscoelasticity and tissue composition of human lateral menisci remains contradictory or completely lacking, the aim of this study was to fill these gaps by comprehensively characterising the biomechanical properties of menisci with regard to the degree of degeneration. DESIGN: Meniscal tissue from 24 patients undergoing a total knee replacement was collected and the degeneration of each region classified according to Pauli et al. For biomechanical characterisation, compression and tensile tests were performed. Additionally, the water content was determined and infrared (IR) spectroscopy was applied to detect changes in the structural composition, particularly of the proteoglycan and collagen content. RESULTS: With an increasing degree of degeneration, a significant decrease of the equilibrium modulus was detected, while simultaneously the water content and the hydraulic permeability significantly increased. However, the tensile modulus displayed a tendency to decrease with increasing degeneration, which might be due to the significantly decreasing amount of collagen content identified by the IR measurements. CONCLUSION: The findings of the current study may contribute to the understanding of meniscus degeneration, showing that degenerative processes appear to mainly worsen viscoelastic properties of the inner circumference by disrupting the collagen integrity.

Osseointegration of titanium implants with a novel silver coating under dynamic loading.

Postoperative implant-associated infections are a severe complication in orthopaedics and trauma surgery. To address this problem, a novel implant coating was recently developed, which allows for the release of low concentrations of bactericidal silver. For an intended use on load-bearing endoprostheses, stable bone integration is required. The aim of the present study was to evaluate the biocompatibility and osseointegration of titanium implants with the novel coating in a mechanically loaded bone-defect model in sheep. Silver-coated devices were implanted into weight-bearing and non-weight-bearing tibial and femoral bone defects whereas, in the control group, uncoated titanium implants were inserted. The bony integration of the implants was assessed mechanically and histologically after 6 months. Silver concentrations were assessed in peripheral blood, liver, kidney and local draining lymph nodes as well as at the implantation site. After 6 months, shear strength at the interface and bone apposition to the implant surface were not significantly different between coated and uncoated devices. Mechanical loading reduced bony integration independently of the coating. Silver content at the implantation site was larger in the group with silver-coated implants, yet it remained below toxic levels and no cytotoxic side effects were observed. Concluding, the novel antibacterial silver coating did not negatively influence bone regeneration or implant integration under mechanically unloaded and even loaded conditions, suggesting that the silver coating might be suitable for orthopaedic load-bearing implants, including endoprostheses.

Optimizing Manufacturing and Osseointegration of Ti6Al4V Implants through Precision Casting and Calcium and Phosphorus Ion Implantation? In Vivo Results of a Large-Scale Animal Trial.

BACKGROUND: Uncemented implants are still associated with several major challenges, especially with regard to their manufacturing and their osseointegration. In this study, a novel manufacturing technique-an optimized form of precision casting-and a novel surface modification to promote osseointegration-calcium and phosphorus ion implantation into the implant surface-were tested in vivo. METHODS: Cylindrical Ti6Al4V implants were inserted bilaterally into the tibia of 110 rats. We compared two generations of cast Ti6Al4V implants (CAST 1st GEN, n = 22, and CAST 2nd GEN, n = 22) as well as cast 2nd GEN Ti6Al4V implants with calcium (CAST + CA, n = 22) and phosphorus (CAST + P, n = 22) ion implantation to standard machined Ti6Al4V implants (control, n = 22). After 4 and 12 weeks, maximal pull-out force and bone-to-implant contact rate (BIC) were measured and compared between all five groups. RESULTS: There was no significant difference between all five groups after 4 weeks or 12 weeks with regard to pull-out force (p > 0.05, Kruskal Wallis test). Histomorphometric analysis showed no significant difference of BIC after 4 weeks (p > 0.05, Kruskal-Wallis test), whereas there was a trend towards a higher BIC in the CAST + P group (54.8% ± 15.2%), especially compared to the control group (38.6% ± 12.8%) after 12 weeks (p = 0.053, Kruskal-Wallis test). CONCLUSION: In this study, we found no indication of inferiority of Ti6Al4V implants cast with the optimized centrifugal precision casting technique of the second generation compared to standard Ti6Al4V implants. As the employed manufacturing process holds considerable economic potential, mainly due to a significantly decreased material demand per implant by casting near net-shape instead of milling away most of the starting ingot, its application in manufacturing uncemented implants seems promising. However, no significant advantages of calcium or phosphorus ion implantation could be observed in this study. Due to the promising results of ion implantation in previous in vitro and in vivo studies, further in vivo studies with different ion implantation conditions should be considered.

Analysis of microscopic bone properties in an osteoporotic sheep model: a combined biomechanics, FE and ToF-SIMS study.

The present study deals with the characterization of bone quality in a sheep model of postmenopausal osteoporosis. Sheep were sham operated ( n = 7), ovariectomized ( n = 6), ovariectomized and treated with deficient diet ( n = 8) or ovariectomized, treated with deficient diet and glucocorticoid injections ( n = 7). The focus of the study is on the microscopic properties at tissue level. Microscopic mechanical properties of osteoporotic bone were evaluated by a combination of biomechanical testing and mathematical modelling. Sample stiffness and strength were determined by compression tests and finite-element analysis of stress states was conducted. From this, an averaged microscopic Young's modulus at tissue level was determined. Trabecular structure as well as mineral and collagen distribution in samples of sheep vertebrae were analysed by micro-computed tomography and time-of-flight secondary ion mass spectrometry. In the osteoporotic sheep model, a disturbed fibril structure in the triple treated group was observed, but bone loss only occurred in form of reduced trabecular number and thickness and cortical decline, while quality of the residual bone was preserved. The preserved bone tissue properties in the osteoporotic sheep model allowed for an estimation of bone strength which behaves similar to the human case.

Histomorphometric Analysis of Callus Formation Stimulated by Axial Dynamisation in a Standardised Ovine Osteotomy Model.

The cyclic axial dynamisation of a stabilised fracture is intended to promote callus formation and bone healing. Most studies focused on biomechanical properties or the quantity of new bone formation. Far less is known about the quality of newly formed callus tissues, such as tissue distribution and arrangement within the callus. The aim of this current study was to investigate the effect of cyclic, axial dynamisation on the quantity and quality of callus in an established delayed fracture healing model. In 41 sheep transverse osteotomies with a gap size of 3 mm were stabilised with a unilateral external fixator. In 32 of these, fracture ends were axially stimulated with displacement amplitudes of 0.8 mm, 0.4 mm, 0.2 mm, or 0.0 mm, respectively, for six weeks. In the remaining 9 sheep of the control group, an additional external fixator was mounted to achieve almost total rigidity. Animal material originating from a past animal experiment was reanalysed in this study. Histological thin-ground sections were histomorphometrically analysed regarding the histological structure and composition of the defect region. A slight tendency towards an increase in size of total callus area, area of new bone (nB.Ar), and cartilage (Cg.Ar) was detected with increasing displacement amplitudes compared to the control group. At the anterior callus side nB.Ar and Cg.Ar were significantly larger than at the posterior side in all groups independent of treatment. Regarding the quality of callus, areas of very compact bone were predominant in the treatment groups whereas in the control group a slight shift to more porous bone was observed. No difference of callus compactness was observed between the anterior and the posterior side. The established method to assess the local compactness of callus areas is a useful tool to quantitatively determine the spatial distribution of new bone tissue within the callus. The application of this method in combination with biomechanical testing might reveal interesting relations between tissue distribution and bone strength that, with traditional histomorphometry, cannot be identified.

Effects of low-magnitude high-frequency vibration on osteoblasts are dependent on estrogen receptor α signaling and cytoskeletal remodeling.

Clinical and experimental studies demonstrate the potential of low-magnitude high-frequency vibration (LMHFV) to enhance bone formation in the intact skeleton and during fracture healing. Moreover, it was shown that the effects of vibration therapy during fracture healing are highly dependent on the estrogen status of the vibrated individual and that estrogen receptor (ER) α signaling plays a major role in mechanotransduction of LMHFV. Because it is known that LMHFV can directly act on osteogenic cells, we hypothesize that the differential effects of LMHFV in the presence and absence of estrogen are mediated by ERα signaling in osteoblasts. To prove this hypothesis, we subjected preosteoblastic MC3T3-E1 cells and primary osteoblasts to LMHFV in vitro. We found increased Cox2 gene expression, cell metabolic activity and cell proliferation after LMHFV in the absence of estrogen, whereas the effects were contrary in the presence of estrogen. Blocking of ERα signaling by Esr1-siRNA knockdown or adding the selective ERα antagonist MPP dihydrochloride abolished the effects of LMHFV on osteoblast proliferation and Cox2 expression. Furthermore, primary osteoblasts isolated from ERα-knockout mice did not show a response towards LMHFV in the presence of estrogen. Additionally, blocking of actin cytoskeletal remodeling by adding the p160ROCK inhibitor Y-27632 abolished the effects of LMHFV. In contrast, expression of primary cilium was not necessary for mechanotransduction of LMHFV. These results suggest that direct effects of LMHFV on osteoblasts are dependent on ERα signaling and cytoskeletal remodeling.

Modelling the fracture-healing process as a moving-interface problem using an interface-capturing approach.

We present a novel numerical model of the fracture-healing process using interface-capturing techniques, a well-known approach from fields like fluid dynamics, to describe tissue growth. One advantage of this method is its direct connection to experimentally observable parameters, including tissue-growth velocities. In our model, osteogenesis, chondrogenesis and revascularisation are triggered by mechanical stimuli via mechano-transduction based on previously established hypothesis of Claes and Heigele. After experimentally verifying the convergence of the numerical method, we compare the predictions of our model with those of the already established Ulm bone-healing model, which serves as a benchmark, and corroborate our results with existing animal experiments. We demonstrate that the new model can predict the history of the interfragmentary movement and forecast a tissue evolution that appears similar to the experimental results. Furthermore, we compare the relative tissue concentration in the healing domain with outcomes of animal experiments. Finally, we discuss the possible application of the model to new fields, where numerical simulations could also prove beneficial.

Calcium and vitamin D in bone fracture healing and post-traumatic bone turnover.

Calcium and vitamin D are essential for maintaining bone health. Therefore, deficiencies in calcium and vitamin D are major risk factors for osteoporosis development. Because sufficient amounts of calcium are also required for fracture-callus mineralisation, compromised bone repair that is frequently observed in osteoporotic patients might be attributed to calcium and vitamin D deficiencies. Consequently, calcium and vitamin D supplementation represents a potential strategy for treating compromised fracture healing in osteoporotic patients. Growing clinical evidence suggests that a fracture event may induce post-traumatic bone loss in the non-fractured skeleton, particularly in osteoporotic patients, which might further exacerbate osteoporosis and increase the risk of secondary fractures. Because the skeleton represents the main source of calcium, which is increasingly required during fracture-callus mineralisation, post-traumatic calcium mobilisation might occur under conditions of insufficient calcium and vitamin D status. However, to date, investigations of the roles of calcium and vitamin D in bone repair and post-traumatic bone turnover are very limited. The current review summarises the state of the literature, focusing on the role of calcium and vitamin D in fracture healing and post-traumatic bone turnover, and critically discusses the therapeutic potential of calcium and vitamin D supplementation in this context.

Neutrophils in Tissue Trauma of the Skin, Bone, and Lung: Two Sides of the Same Coin.

Following severe tissue injury, patients are exposed to various danger- and microbe-associated molecular patterns, which provoke a strong activation of the neutrophil defense system. Neutrophils trigger and modulate the initial posttraumatic inflammatory response and contribute critically to subsequent repair processes. However, severe trauma can affect central neutrophil functions, including circulation half-life, chemokinesis, phagocytosis, cytokine release, and respiratory burst. Alterations in neutrophil biology may contribute to trauma-associated complications, including immune suppression, sepsis, multiorgan dysfunction, and disturbed tissue regeneration. Furthermore, there is evidence that neutrophil actions depend on the quality of the initial stimulus, including trauma localization and severity, the micromilieu in the affected tissue, and the patient's overall inflammatory status. In the present review, we describe the effects of severe trauma on the neutrophil phenotype and dysfunction and the consequences for tissue repair. We particularly concentrate on the role of neutrophils in wound healing, lung injury, and bone fractures, because these are the most frequently affected tissues in severely injured patients.

A new TAO kinase inhibitor reduces tau phosphorylation at sites associated with neurodegeneration in human tauopathies.

In Alzheimer's disease (AD) and related tauopathies, the microtubule-associated protein tau is highly phosphorylated and aggregates to form neurofibrillary tangles that are characteristic of these neurodegenerative diseases. Our previous work has demonstrated that the thousand-and-one amino acid kinases (TAOKs) 1 and 2 phosphorylate tau on more than 40 residues in vitro. Here we show that TAOKs are phosphorylated and active in AD brain sections displaying mild (Braak stage II), intermediate (Braak stage IV) and advanced (Braak stage VI) tau pathology and that active TAOKs co-localise with both pre-tangle and tangle structures. TAOK activity is also enriched in pathological tau containing sarkosyl-insoluble extracts prepared from AD brain. Two new phosphorylated tau residues (T123 and T427) were identified in AD brain, which appear to be targeted specifically by TAOKs. A new small molecule TAOK inhibitor (Compound 43) reduced tau phosphorylation on T123 and T427 and also on additional pathological sites (S262/S356 and S202/T205/S208) in vitro and in cell models. The TAOK inhibitor also decreased tau phosphorylation in differentiated primary cortical neurons without affecting markers of synapse and neuron health. Notably, TAOK activity also co-localised with tangles in post-mortem frontotemporal lobar degeneration (FTLD) brain tissue. Furthermore, the TAOK inhibitor decreased tau phosphorylation in induced pluripotent stem cell derived neurons from FTLD patients, as well as cortical neurons from a transgenic mouse model of tauopathy (Tau35 mice). Our results demonstrate that abnormal TAOK activity is present at pre-tangles and tangles in tauopathies and that TAOK inhibition effectively decreases tau phosphorylation on pathological sites. Thus, TAOKs may represent a novel target to reduce or prevent tau-associated neurodegeneration in tauopathies.

Janus face of complement-driven neutrophil activation during sepsis.

During local and systemic inflammation, the complement system and neutrophil granulocytes are activated not only by pathogens, but also by released endogenous danger signals. It is recognized increasingly that complement-mediated neutrophil activation plays an ambivalent role in sepsis pathophysiology. According to the current definition, the onset of organ dysfunction is a hallmark of sepsis. The preceding organ damage can be caused by excessive complement activation and neutrophil actions against the host, resulting in bystander injury of healthy tissue. However, in contrast, persistent and overwhelming inflammation also leads to a reduction in neutrophil responsiveness as well as complement components and thus may render patients at enhanced risk of spreading infection. This review provides an overview on the molecular and cellular processes that link complement with the two-faced functional alterations of neutrophils in sepsis. Finally, we describe novel tools to modulate this interplay beneficially in order to improve outcome.

Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells.

Thousand-and-one amino acid kinases (TAOK) 1 and 2 are activated catalytically during mitosis and can contribute to mitotic cell rounding and spindle positioning. Here, we characterize a compound that inhibits TAOK1 and TAOK2 activity with IC50 values of 11 to 15 nmol/L, is ATP-competitive, and targets these kinases selectively. TAOK inhibition or depletion in centrosome-amplified SKBR3 or BT549 breast cancer cell models increases the mitotic population, the percentages of mitotic cells displaying amplified centrosomes and multipolar spindles, induces cell death, and inhibits cell growth. In contrast, nontumorigenic and dividing bipolar MCF-10A breast cells appear less dependent on TAOK activity and can complete mitosis and proliferate in the presence of the TAOK inhibitor. We demonstrate that TAOK1 and TAOK2 localize to the cytoplasm and centrosomes respectively during mitosis. Live cell imaging shows that the TAOK inhibitor prolongs the duration of mitosis in SKBR3 cells, increases mitotic cell death, and reduces the percentages of cells exiting mitosis, whereas MCF-10A cells continue to divide and proliferate. Over 80% of breast cancer tissues display supernumerary centrosomes, and tumor cells frequently cluster extra centrosomes to avoid multipolar mitoses and associated cell death. Consequently, drugs that stimulate centrosome declustering and induce multipolarity are likely to target dividing centrosome-amplified cancer cells preferentially, while sparing normal bipolar cells. Our results demonstrate that TAOK inhibition can enhance centrosome declustering and mitotic catastrophe in cancer cells, and these proteins may therefore offer novel therapeutic targets suitable for drug inhibition and the potential treatment of breast cancers, where supernumerary centrosomes occur. Mol Cancer Ther; 16(11); 2410-21. ©2017 AACR.

Friction properties of a new silk fibroin scaffold for meniscal replacement.

The menisci protect the articular cartilage by reducing contact pressure in the knee. To restore their function after injury, a new silk fibroin replacement scaffold was developed. To elucidate its tribological properties, friction of the implant was tested against cartilage and glass, where the latter is typically used in tribological cartilage studies. The silk scaffold exhibited a friction coefficient against cartilage of 0.056, which is higher than meniscus against cartilage but in range of the requirements for meniscal replacements. Further, meniscus friction against glass was lower than cartilage against glass, which correlated with the surface lubricin content. Concluding, the tribological properties of the new material suggest a possible long-term chondroprotective function. In contrast, glass always produced high, non-physiological friction coefficients.

Influence of tibial hybrid fixation on graft tension and stability in ACL double-bundle reconstruction.

PURPOSE: Initial graft tension in anterior cruciate ligament (ACL) reconstruction affects stability and tension loss at follow-up. This study investigated the influence of hybrid tibial fixation in 3-tunnel double-bundle ACL reconstruction on initial graft tension and tension change and stability under anterior and combined rotatory loads. METHODS: Eleven fresh-frozen cadaveric knees were reconstructed with an ACL double bundle using a 3-tunnel technique. Grafts were tightened to 80 N in 60° (AM bundle) and 15° (PL bundle) of flexion. Anterior tibial translation under 134 N of anterior shear load and translation under combined rotatory and valgus loads (10 Nm valgus stress, 4 Nm internal tibial torque) were determined at 0°, 30°, 60°, and 90° flexion. In addition, graft tension under continuous passive motion was determined. Intact, ACL-resected and ACL-reconstructed joints with either tibial extracortical graft fixation or extracortical plus supplemental aperture graft fixation (hybrid fixation) were tested. RESULTS: Hybrid fixation did not increase graft tension in either bundle during fixation or in motion without additional load. AM-bundle tension increased (p < 0.05) at 0° under combined rotatory and valgus loads and at 30° and 60° under both loading conditions without decreasing the anterior tibial translation. PL-bundle tension increased (p < 0.05) only at 90° under combined rotatory and valgus loads. CONCLUSIONS: Tibial hybrid fixation in 3-tunnel double-bundle ACL reconstruction increases time-zero AM- and PL-bundle tensions under loading conditions, generating greater construct stiffness. This could lead to a longer preservation of ACL-graft stability in clinical follow-up before bony incorporation.

Hepatic Lipodystrophy in Galloway Calves.

Hepatic lipodystrophy in Galloway calves is a fatal liver disease affecting a small proportion of the Galloway breed described in different parts of Europe and North America during the past decades. The clinical findings include a diversity of neurological signs. Clinical pathology findings frequently indicate hepatobiliary disease. Postmortem examination reveals an enlarged, pale yellow, and firm liver. Histologic lesions include hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. To date, the etiopathogenesis remains obscure. Infectious causes, intoxications, and a hereditary origin have been considered. We describe hepatic lipodystrophy in Galloway calves from an extensively farmed cow-calf operation in southern Germany. Main clinical findings in 6 calves were consistent with hepatic encephalopathy. Clinical pathology findings in 5 of 6 tested animals revealed increased concentration of total bilirubin (maximum value [MV], 54 µmol/l; reference range [RR], <8.5 µmol/l), direct bilirubin (MV, 20 µmol/l; RR, <3.4 µmol/l), increased activity of gamma glutamyl transferase (MV, 162 U/l; RR, <36 U/l) and glutamate dehydrogenase (MV, 420 U/l; RR, <16 U/l). In addition, activity of glutathione peroxidase was decreased in all tested ( n = 5) animals (MV, 61 U/g hemoglobin [Hb]; RR, >250 U/g Hb). Postmortem examination in 6 calves revealed a firm, diffusely enlarged yellow liver with a finely nodular surface. Histologic lesions included hepatic fibrosis, hepatic lipidosis, and bile duct hyperplasia. Our findings add to the existing data on hepatic lipodystrophy in the Galloway breed and outline a protocol to aid in the diagnosis of this disorder.