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In drug development, assessing the toxicity of candidate compounds is crucial for successfully transitioning from preclinical research to early-stage clinical trials. Drug safety is typically assessed using animal models with a manual histopathological examination of tissue sections to characterize the dose-response relationship of the compound - a time-intensive process prone to inter-observer variability and predominantly involving tedious review of cases without abnormalities. Artificial intelligence (AI) methods in pathology hold promise to accelerate this assessment and enhance reproducibility and objectivity. Here, we introduce TRACE, a model designed for toxicologic liver histopathology assessment capable of tackling a range of diagnostic tasks across multiple scales, including situations where labeled data is limited. TRACE was trained on 15 million histopathology images extracted from 46,734 digitized tissue sections from 157 preclinical studies conducted on Rattus norvegicus . We show that TRACE can perform various downstream toxicology tasks spanning histopathological response assessment, lesion severity scoring, morphological retrieval, and automatic dose-response characterization. In an independent reader study, TRACE was evaluated alongside ten board-certified veterinary pathologists and achieved higher concordance with the consensus opinion than the average of the pathologists. Our study represents a substantial leap over existing computational models in toxicology by offering the first framework for accelerating and automating toxicological pathology assessment, promoting significant progress with faster, more consistent, and reliable diagnostic processes.

Monitoring neoplasms in standardized registries facilitates epidemiologic studies of risk factors for tumor development and predisposition. In an observational study, we determined incidence rates (IR) and malignant tumor incidence rate ratios (IRR) by age, sex, and breed in Swiss dogs using demographic data from the official Swiss dog registration database Amicus. The dataset analyzed included 54'986 tumors diagnosed by histology and cytology in four Swiss veterinary pathology laboratories between 2008 and 2020. Diagnoses were coded according to the Vet-ICD-O-canine-1 system. Most tumors occurred in the skin (n = 19'045; 34.64%), soft tissues (n = 11'092; 20.17%), and mammary glands (n = 7'974; 14.50%). The IRs for all and for malignant tumors were 775/100'000 dog-years at risk (95%CI 764-777) and 338/100'000 dog-years at risk (95%CI 333-342), respectively. Females (850; 95%CI 834-853) had a higher overall tumor IR than males (679; 95%CI 666-684). The highest tumor IR was found at 11 years of age (1'857; 95%CI 1'780-1'867). Potential novel breed-specific predispositions were uncovered, with high IRs for several benign and malignant tumors in Polski Owczarek Nizinnys (overall IR: 3'303; 95%CI 2'502-3'864) and high IRs for malignant tumors in Russian Black Terriers (melanomas: 345; 95%CI 138-708), Field Spaniels (adenocarcinomas: 376; CI95% 138-817), Dogo Argentinos (mast cell tumors: 844; CI95% 591-1'169), King Charles Spaniels and Manchester Terriers (lymphomas: 319; CI95% 137-627 and 302; CI95% 98-704, respectively), Landseers (osteosarcomas: 74; CI95% 15-216), Bouvier des Flandres (hemangiosarcomas: 127; CI95% 26-371), and Bearded Collies and Cane Corso Italianos (gliomas: 91; CI95% 45-162 and 34; CI95% 7-99, respectively). Nordic hunting dogs had the highest (8.08; CI95% 3.55-16.7) and Chihuahueno the lowest cancer IRRs (0.42; 95%CI 0.31-0.57) compared to mixed breeds. In conclusion, the calculated IRs and IRRs revealed previously unknown predisposing factors, including novel breed-specific susceptibilities. The results may have implications for cancer screening, diagnostic work-up, breeding management and oncologic and translational research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dhein et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Soft tissue tumors/sarcomas (STSs) in felines, encompassing a variety of mesenchymal tumors with similar histomorphological features, present diagnostic challenges due to their diverse cellular origins and the overlap with other tumor types such as feline sarcoid. This study aimed to delineate the clinical, histomorphological, and immunohistochemical characteristics of 34 feline facial spindle cell tumors affecting 29 cats, including testing for bovine papillomavirus type 14 (BPV14), the virus causing feline sarcoids. Only five out of 12 tumors previously diagnosed as feline sarcoids based on histomorphology were confirmed by PCR for BPV14, underscoring the importance of comprehensive diagnostic approaches to accurately distinguish between STSs and feline sarcoids. This study shows that most facial spindle cell tumors were compatible with peripheral nerve sheath tumors (PNSTs) based on positive immunohistochemical staining for Sox10 and other immunohistochemical markers such as GFAP, NSE, and S100. Some of these tumors displayed as multiple independent masses on the face or as erosive and ulcerative lesions without obvious mass formation, an atypical presentation and an important highlight for general practitioners, dermatologists, and oncologists. This study also describes periadnexal whorling of neoplastic cells as a novel histomorphologic finding in feline facial PNSTs and emphasizes Sox10 as a useful complementary immunohistochemical marker for the diagnosis of facial PNST in cats, providing valuable insights for veterinary pathologists.

Background: The importance of meniscal repair is widely accepted because of the association of loss of meniscal tissue with the development of early-onset knee arthritis. Many factors influencing the results of meniscal repair have been reported, but results remain controversial., Purpose: This meta-analysis determines the pooled meniscal repair failure rate of studies with a minimum follow-up of 2 years up to 5 years, with a mean follow-up of 43 months. Moreover, selected failure-influencing factors are analyzed., Study Design: Systematic review and meta-analysis; Level of evidence, 4., Methods: PubMed and Scopus were searched for studies published between January 2000 and November 2021 reporting on meniscal repair outcome with a minimum follow-up of 24 months. The overall pooled failure rate and pooled failure rates for possible predictors were calculated. Random-effect models were used to pool failure rates, and effect estimates in the form of odds ratios with 95% CIs were established., Results: The initial literature search identified 6519 studies. A total of 51 studies met the inclusion criteria. In total, 3931 menisci were included with an overall failure rate of 14.8%. Subgroup analysis revealed a significantly lower failure rate for meniscal repair with concomitant anterior cruciate ligament (ACL) reconstruction compared with knees without any reported injury to the ACL (8.5% vs 14%; P = .043). The pooled failure rate for lateral meniscal repair was significantly lower than that for medial meniscal repair (6.1% vs 10.8%; P = .031). Pooled failure rates of all-inside and inside-out repair were not significantly different (11.9% vs 10.6%; P > .05)., Conclusion: This meta-analysis on close to 4000 patients demonstrates an overall meniscal repair failure rate of 14.8% at a minimum follow-up from 2 years up to 5 years. Meniscal repair remains a procedure with a high failure rate, especially within the first 2 postoperative years. This review and meta-analysis also identified clinically relevant factors associated with favorable outcomes such as concomitant ACL reconstruction or repair of the lateral meniscus. All-inside meniscal repair with the latest-generation devices yields failure rates of <10%. The failure mechanism and the time of failure is poorly documented; further studies are needed for a better understanding of the retear mechanism., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: R.W. has received consulting fees from Johnson & Johnson Medical and Stryker. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Introduction: Diseases of the digits often occur in cattle on larger cattle mountain pastures. In the late spring 2020, at the time of the ascent of 1554 cattle to 11 high altitude alpine pastures in the Lower Engadine region, lesions in the area of the digits were clinically assessed and documented. 254 cattle were of non-cantonal and 1300 of local origin (Lower Engadine; postal code CH-75XX). Skin lesions in the area of the digits, identified as digital dermatitis (DD; Mortellaro's disease), were further classified according to the DD scoring system. Nonspecific skin lesions with clinical evidence of granulation tissue formation were termed chronic penetrating skin lesions (CPSL). At the end of the alpine pasturing season, in the early fall (descent of cattle from the alpine pastures), the procedure was repeated, and biopsies were taken from randomly selected cattle with CPSL. Digital dermatitis lesions were found in 34 of 1551 cattle at ascent, but no case of CPSL was found at that time. At descent, 19 of 1529 cattle had DD lesions and 88 cattle had CPSL. The clinical appearance of the CPSL was consistent with chronic skin lesions caused by penetrating skin lacerations. Histologically, the majority of the CPSL were classified as chronic hyperplastic dermatitis with granulation tissue formation. In all CPSL biopsies examined by PCR, Fusobacterium necrophorum and Porphyromonas levii, but neither Dichelobacter nodosus nor the tested Treponema species were detected. Fluorescence in situ hybridization revealed a negative result for Treponema species in all biopsies. In the regression analysis, cattle in the age group of 365 to 730 days had an increased risk for the presence of CPSL compared to the age group of 160 to 365 days (odds ratio (OR) = 4,95; confidence interval (CI) = 1,97-12,43). Holstein cattle had an increased risk of developing CPSL compared to Brown cattle (OR = 2,92; CI = 1,46-5,86) and cattle of non-cantonal origin showed a massively higher risk compared to local cattle (OR = 10,59; CI = 5,79 - 19,37). The statistically significant associations found in the present study can be taken into account in the selection of animals for summer pasturing on high altitudes in the future in order to reduce the prevalence of CPSL and consequently reduce the antimicrobial use. Spread of DD during the alpine pasturing season within the cattle groups examined was not found.

Fungal periprosthetic joint infections (PJI) are difficult to treat, due to important biofilm formation and limited local penetration of systemically administered antifungals. Calcium sulphate (CaSO 4 ) might be a promising carrier to increase local concentration of antifungals. We hypothesized that local amphotericin B release from CaSO 4 is high enough to significantly contribute to treatment of fungal PJI. We report joint fluid and serum concentrations of amphotericin B after local application with CaSO 4 as an implanted resorbable carrier material as adjunct to standard surgical and systemic antifungal treatment in two cases of PJI with Candida spp. Maximal joint fluid amphotericin B concentration was 14.01 mg/L 5 days after the second local administration of liposomal amphotericin in Case One and 25.77 mg/L 14 days after the second local administration in Case Two. Concentrations higher than minimal inhibitory concentrations (MIC) could be measured for 21 days and 17 days after local administration in Case One and Two, respectively. In Case Two, serum concentration of amphotericin B was <0.01 mg/L 3 days after local administration of 450 mg liposomal amphotericin B. No local or systemic adverse reaction was observed. Fungal PJI was successfully eradicated in both cases with a follow-up of 12 months in Case One and 20 months in Case Two. Application of amphotericin B-loaded CaSO 4 was associated with joint fluid concentrations higher than minimal inhibitory concentrations for Candida spp. for approximately 3 weeks, with the advantage that the carrier material dissolves spontaneously and does not require secondary removal. Relapse of fungal infections did not occur in these two patients., (© 2022 The Authors. APMIS published by John Wiley & Sons Ltd on behalf of Scandinavian Societies for Pathology, Medical Microbiology and Immunology.)

Background: Persistent instability of the knee is reported in up to 30% of patients after anterior cruciate ligament (ACL) reconstruction. Based on anatomic findings showing that ACL is a flat ribbon-like structure that twists during knee flexion, a new surgical ACL reconstruction technique using a ribbon-like graft has been developed. However the effect of this surgical technique on knee kinematics has not yet been evaluated., Purpose: To compare the anteroposterior and rotational stability of the knee after ACL reconstruction using single-bundle (SB) round and ribbon-like grafts in anterolateral-intact/deficient knees., Study Design: Controlled laboratory study., Methods: Twelve human fresh-frozen cadaveric knees were tested with a 6 degrees of freedom robotic system. Internal rotation and anterior translation of the knee were recorded from 0° to 90° of flexion. A full kinematic assessment was performed in each of the following conditions: (1) intact knee, (2) after sectioning of the ACL, (3) after ACL reconstruction using a SB hamstring tendon graft in a round configuration and a ribbon-like configuration, and (4) after sectioning of the anterolateral structures. One-way analysis of variance and post hoc Tukey tests were used for statistical analyses., Results: When compared with the intact knee, the ACL-deficient knee demonstrated a mean ± SD increase in anterior translation and internal rotation of 6.3 ± 2.5 mm ( P < .01) and 5.8°± 2.3° ( P < .01), respectively. After ACL reconstruction using a SB ribbon-like graft, the mean difference in anterior translation and internal rotation as compared with the intact knee was -0.1 ± 1.5 mm ( P = .842) and 0.0°± 1.1° ( P = .999). These differences from the intact knee were also not significant after ACL reconstruction using a round graft (-0.1 ± 1.3 mm, P = .999; -0.5°± 1.5°, P = .401). In the ACL-reconstructed knee using either a ribbon-like or round graft, sectioning of the anterolateral structures did not induce a significant increase of anterior translation and internal rotation of the knee., Conclusion: ACL reconstruction using a SB ribbon-like or round graft restored the kinematics of the intact knee at time zero. Secondary sectioning of the anterolateral structures in the ACL-reconstructed knee using both types of graft did not significantly affect the anterior translation and internal rotation of the knee., Clinical Relevance: This is the first biomechanical study on the new ACL reconstruction technique using a ribbon-like graft.

Introduction: With every surgical procedure there is a risk of postoperative infection (surgical site infection = SSI). This risk of infection can be influenced by various factors, including perioperative antibiotic prophylaxis. In terms of antibiotic stewardship, antibiotics should only be used if there is a proven benefit for the patient. However, this advantage has not yet been conclusively proven, especially for clean and clean-contaminated surgeries. The aim of our study was to document various relevant influencing factors on the infection rate after clean and clean-contaminated surgeries in dogs and cats. In particular, it was documented to what extent a reduced use of antibiotics affects the infection rate in the context of all influencing factors. Over a period of eleven months, 807 clean and clean-contaminated surgeries in dogs and cats were prospectively analyzed with possible influencing factors (gender, ASA classification, underlying endocrinological diseases, duration of anesthesia, duration of surgery, type of surgery, perioperative antibiotic prophylaxis (POA), duration of hospitalization) affecting the infection rate. After surgery all cases were followed up either 30 or 90 days, if implants were used. The effect of the various factors was evaluated using multivariable logistic regression analysis. SSI was detected in 25/664 clean and 10/143 clean-contaminated surgeries. Longer hospitalization, without antimicrobial prophylaxis, and male animals had a significantly higher risk of SSI. In clean surgeries, SSI occurred in 2,3 % of all cases with POA and 5,3 % without POA. The SSI in clean-contaminated was 3,6 % with POA and 9 % without. This difference resulted mainly from the results of osteosynthesis, gastrointestinal and skin surgeries. However, other types of surgeries, such as castrations, neurological interventions, abdominal and thoracic surgeries, and surgeries in the head and neck region, showed comparable infection rates with and without POA.

Equine sarcoids (ES) were diagnosed in 12 Somali wild asses (SWA) ( Equus africanus somaliensis ) from 10 different institutions of the SWA European Endangered Species Programme from 1976 to 2019. Samples of surgically excised masses, biopsies, or necropsy samples were submitted for histologic and virologic analysis. In addition, tissue samples from one onager ( Equus hemionus onager ), one kulan ( Equus hemionus kulan ), and two Hartmann's mountain zebras (HMZ) ( Equus zebra hartmannae ) were examined. Histology confirmed the diagnosis of ES exhibiting the typical microscopic features. Polymerase chain reaction detected bovine papillomavirus type 1 (BPV1) DNA in eight SWA samples and bovine papillomavirus type 2 (BPV2) DNA in one SWA sample. The onager, kulan, and one HMZ sample tested positive for BPV1. The other HMZ tested positive for BPV1 and BPV2. This is the first report of ES in an onager. Surgical excision was the treatment elected by most veterinarians. A follow-up survey of the cases over several years after clinical diagnosis and therapy revealed variable individual outcome with ES recurrence in four cases. Three SWA and the kulan were euthanized due to the severity of the lesions. Nine affected SWA were males with seven having a sarcoid located at the prepuce. Because a genetic disposition is a risk factor for the development of ES in horses, this may also be true for endangered wild equids with few founder animals in their studbook history. Innovative approaches regarding therapy and prevention of ES in wild equids are therefore highly encouraged.

Several outbreaks of necrotic enteritis-like disease in lorikeets, from which Clostridium perfringens was consistently isolated, are described. All lorikeets had acute, segmental, or multifocal fibrinonecrotizing inflammatory lesions in the small and/or the large intestine, with intralesional gram-positive rods. The gene encoding C. perfringens alpha toxin was detected by PCR (polymerase chain reaction) on formalin-fixed, paraffin-embedded (FFPE) tissues in 20 out of 24 affected lorikeets (83%), but it was not amplified from samples of any of 10 control lorikeets ( P < .0001). The second most prevalent C. perfringens toxin gene detected was the beta toxin gene, which was found in FFPE from 7 out of 24 affected lorikeets (29%). The other toxin genes were detected inconsistently and in a relatively low number of samples. These cases seem to be associated with C. perfringens , although the specific type involved could not be determined.

Purpose: To determine the stabilizing role of anterolateral ligament reconstruction (ALLR) and modified Lemaire lateral extra-articular tenodesis (LET) performed in combination with anterior cruciate ligament reconstruction (ACLR) and to determine whether either procedure was superior to the other., Methods: Six nonpaired, human, fresh-frozen cadaveric knees were tested with a 6-df robotic system. Internal rotation and anterior translation of the knee were recorded from 0° to 90° of flexion after application of a 5-Nm internal rotation torque and a 134-N anterior load, respectively. A full kinematic assessment was performed in each of the following conditions: (1) intact knee, (2) after sectioning of the anterior cruciate ligament (ACL), (3) after sectioning of the ACL and anterolateral ligament, (4) after isolated ACLR, and (5) after combined ACLR and Lemaire LET and combined ACLR and ALLR. ALLR was performed using the gracilis tendon, whereas the modified Lemaire procedure was performed using the central strip of the iliotibial band. The different states were compared using a Tukey paired comparison test., Results: In knees with combined deficiency of the ACL and anterolateral structures, anterior translation and internal rotation remained significantly increased after isolated ACLR compared with the intact knee (+2.33 ± 1.44 mm and +1.98° ± 1.06°, respectively; P < .01). On the other hand, the addition of ALLR or modified Lemaire LET to ACLR restored anterior translation and internal rotation to values similar to those in the intact knee. The 2 anterolateral procedures did not show statistically significantly different values for both tests. This difference was 0.67 ± 1.46 mm for anterior translation (P = .79) and 0.11° ± 1.11° for internal rotation (P = .99)., Conclusions: In knees with ACL and anterolateral deficiency, combined ACLR and anterolateral reconstruction restored the native knee stability in anterior translation and internal rotation contrary to isolated ACLR. In addition, both types of extra-articular reconstruction-ALLR and modified Lemaire LET-were similar in terms of restoring knee kinematics, and neither overconstrained the knee., Clinical Relevance: In knees with deficiency of the ACL and anterolateral structures, combined ACLR and anterolateral reconstruction increased knee stability at time zero after surgery. This biomechanical improvement could be responsible for the protective effect on ACL graft and meniscal repair reported in the literature after the combined procedure., (Copyright © 2020 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Poly(ADP-ribose) polymerase inhibition (PARPi) is a promising new therapeutic approach for the treatment of cancers that show homologous recombination deficiency (HRD). Despite the success of PARPi in targeting HRD in tumors that lack the tumor suppressor function of BRCA1 or BRCA2, drug resistance poses a major obstacle. We developed three-dimensional cancer organoids derived from genetically engineered mouse models (GEMMs) for BRCA1- and BRCA2-deficient cancers. Unlike conventional cell lines or mammospheres, organoid cultures can be efficiently derived and rapidly expanded in vitro. Orthotopically transplanted organoids give rise to mammary tumors that recapitulate the epithelial morphology and preserve the drug response of the original tumor. Notably, GEMM-tumor-derived organoids can be easily genetically modified, making them a powerful tool for genetic studies of tumor biology and drug resistance.

Purpose: We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse. Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53 -mutant breast cancer. Because of the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore, no BRCA1-dependent acquired resistance occurs. To characterize the cell-cycle stage from which Brca1 -/- ;p53 -mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single-nucleated cells delaying entry into the S-phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct, we identified nonfluorescent G -/- mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell-cycle indicator (FUCCI) construct into the tumor cells. Results: Despite repeated sensitivity to the MTD of platinum drugs, the Brca1 -mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single-nucleated cells delaying entry into the S-phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct, we identified nonfluorescent G 0 -like cells as the population most tolerant to platinum drugs. Intriguingly, these cells are more sensitive to the DNA-crosslinking agent nimustine, resulting in an increased number of multinucleated cells that lack clonogenicity. This is consistent with our in vivo finding that the nimustine MTD, among several alkylating agents, is the most effective in eradicating Brca1 -mutated mouse mammary tumors. Conclusions: Our data show that targeting G 0 -like cells is crucial for the eradication of BRCA1/p53-deficient tumor cells. This can be achieved with selected alkylating agents such as nimustine. Clin Cancer Res; 23(22); 7020-33. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Mutations in homologous recombination (HR) genes BRCA1 and BRCA2 predispose to tumorigenesis. HR-deficient cancers are hypersensitive to Poly (ADP ribose)-polymerase (PARP) inhibitors, but can acquire resistance and relapse. Mechanistic understanding how PARP inhibition induces cytotoxicity in HR-deficient cancer cells is incomplete. Here we find PARP inhibition to compromise replication fork stability in HR-deficient cancer cells, leading to mitotic DNA damage and consequent chromatin bridges and lagging chromosomes in anaphase, frequently leading to cytokinesis failure, multinucleation and cell death. PARP-inhibitor-induced multinucleated cells fail clonogenic outgrowth, and high percentages of multinucleated cells are found in vivo in remnants of PARP inhibitor-treated Brca2 -/- ;p53 -/- and Brca1 -/- ;p53 -/- mammary mouse tumours, suggesting that mitotic progression promotes PARP-inhibitor-induced cell death. Indeed, enforced mitotic bypass through EMI1 depletion abrogates PARP-inhibitor-induced cytotoxicity. These findings provide insight into the cytotoxic effects of PARP inhibition, and point at combination therapies to potentiate PARP inhibitor treatment of HR-deficient tumours.

Objectives: To evaluate the impact of slice-encoding for metal artefact correction (SEMAC) on image quality, findings, and therapy decision in patients with unicompartmental knee arthroplasty (UKA)., Methods: Forty-five painful UKAs were examined at 1.5T-MRI (STIR, proton-density(PD)-weighted sequence, each with SEMAC and high-bandwidth). Artefact size, image quality, anatomic depiction, and clinically relevant findings were compared between SEMAC and high-bandwidth (2 readers). In 30 patients, therapy decision was retrospectively assessed by two orthopaedic surgeons without MRI, with high-bandwidth-MRI, and with SEMAC-MRI., Results: SEMAC reduced mean artefact size for STIR (11.8 cm(2) vs. 37.7 cm(2)) and PD (16.8 cm(2) vs. 18.9 cm(2)), p < 0.0005 for both comparisons. SEMAC showed more blurring than high-bandwidth, p < 0.0005. STIR-SEMAC revealed more bone marrow oedema (29 vs. 18 patients, p = 0.001, 30 vs. 13 patients, p < 0.0005, for reader 1 and 2 respectively). PD-SEMAC was worse in detecting meniscal lesions (6 missed, p = 0.031, 9 missed, p = 0.004, by reader 1 and 2 respectively) than PD-high-bandwidth. Revision-surgery was chosen in 12 and 11 patients without MRI (surgeon 1 and 2), with high-bandwidth-MRI in 15 and 14 patients, and with SEMAC-MRI in 19 and 14 patients., Conclusions: STIR-SEMAC was useful in detecting bone marrow oedema and influenced the orthopaedic surgeons' decisions towards surgery, while PD-SEMAC showed no clinical benefit., Key Points: • Slice-encoding for metal artefact correction (SEMAC) MRI reduces metal-induced artefact size. • STIR SEMAC detects more bone marrow oedema in painful unicompartmental knee arthroplasty. • STIR SEMAC can help the orthopaedic surgeon with decision making. • PD SEMAC suffers from blurring of images, potentially masking relevant meniscal lesions. • PD SEMAC does not improve cartilage lesion detection in the non-operated compartments.

Minimal residual disease (MRD) is a major hurdle in the eradication of malignant tumors. Despite the high sensitivity of various cancers to treatment, some residual cancer cells persist and lead to tumor recurrence and treatment failure. Obvious reasons for residual disease include mechanisms of secondary therapy resistance, such as the presence of mutant cells that are insensitive to the drugs, or the presence of cells that become drug resistant due to activation of survival pathways. In addition to such unambiguous resistance modalities, several patients with relapsing tumors do not show refractory disease and respond again when the initial therapy is repeated. These cases cannot be explained by the selection of mutant tumor cells, and the precise mechanisms underlying this clinical drug resistance are ill-defined. In the current review, we put special emphasis on cell-intrinsic and -extrinsic mechanisms that may explain mechanisms of MRD that are independent of secondary therapy resistance. In particular, we show that studying genetically engineered mouse models (GEMMs), which highly resemble the disease in humans, provides a complementary approach to understand MRD. In these animal models, specific mechanisms of secondary resistance can be excluded by targeted genetic modifications. This allows a clear distinction between the selection of cells with stable secondary resistance and mechanisms that result in the survival of residual cells but do not provoke secondary drug resistance. Mechanisms that may explain the latter feature include special biochemical defense properties of cancer stem cells, metabolic peculiarities such as the dependence on autophagy, drug-tolerant persisting cells, intratumoral heterogeneity, secreted factors from the microenvironment, tumor vascularization patterns and immunosurveillance-related factors. We propose in the current review that a common feature of these various mechanisms is cancer cell dormancy. Therefore, dormant cancer cells appear to be an important target in the attempt to eradicate residual cancer cells, and eventually cure patients who repeatedly respond to anticancer therapy but lack complete tumor eradication., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Bovine tuberculosis (bTB) is a (re-)emerging disease in European countries, including Switzerland. This study assesses the seroprevalence of infection with Mycobacterium bovis and closely related agents in wild boar (Sus scrofa) in Switzerland, because wild boar are potential maintenance hosts of these pathogens. The study employs harmonised laboratory methods to facilitate comparison with the situation in other countries. Eighteen out of 743 blood samples tested seropositive (2.4%, CI: 1.5-3.9%) by ELISA, and the results for 61 animals previously assessed using culture and PCR indicated that this serological test was not 100% specific for M. bovis, cross-reacting with M. microti. Nevertheless, serology appears to be an appropriate test methodology in the harmonisation of wild boar testing throughout Europe. In accordance with previous findings, the low seroprevalence found in wild boar suggests wildlife is an unlikely source of the M. bovis infections recently detected in cattle in Switzerland. This finding contrasts with the epidemiological situation pertaining in southern Spain., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Procalcitonin (PCT) is a useful surrogate marker for the differentiation of postoperative infection and unspecific inflammatory reaction after surgery. It is known that postoperative course of the PCT serum level varies with type of surgery. No data exists about the postoperative course of serum PCT levels after primary total hip replacement (THR)., Purpose: To characterize early postoperative serum PCT levels in uneventful primary THR compared to postoperative levels of different frequently used inflammatory blood parameters., Method: We prospectively investigated 31 patients. Blood samples were taken preoperatively and for 5 days postoperatively. PCT levels were compared with C-reactive protein (CRP), interleukin-6 (IL-6), and blood leucocyte counts (WBC)., Results: In uneventful THR PCT levels showed a uniform low-level course with a peak at the second postoperative day. At the fifth day values returned to almost preoperative levels. On contrary, CRP levels remained high during the entire observational period. Only IL-6 levels showed a peak at postoperative day one with a quick and uniform return to preoperative levels., Conclusion: Similar to observations in cardiothoracic, intestinal, and neural surgeries, postoperative course of PCT after primary THR showed a uniform low-level course with a peak at the second postoperative day but below expected levels in systemic infections.

Background: Hindfoot trauma including ankle and subtalar sprains may be followed by osteochondral lesions and persisting pain originating from posttraumatic arthritis., Hypothesis: "Acute severe" supination sprains and "mild supination sprains with increasing ligamentous incompetence" of the hindfoot lead to medial ankle and subtalar stress concentrations that may contribute to osteochondral lesions (OCLs) and subsequent arthritis., Study Design: Controlled laboratory study., Methods: "Acute severe" sprains and "mild sprains with increasing ligamentous incompetence" (consecutive anterior talofibular ligament [ATFL], calcaneofibular ligament [CFL], and lateral talocalcaneal ligament [LTCL] transections) were simulated in human lower leg specimens (7 different specimens for each condition). The effect on the migration of the center of force (COF) and on the tibiotalar and subtalar pressures at 700-N (acute severe) and 150-N (mild sprain with increasing ligamentous incompetence) axial static and dynamic loads, respectively, was recorded using pressure sensors., Results: In the "acute severe" sprain, the peak pressure increase reached the level of significance in the ankle (P = .042) and in the subtalar medial facet (P = .046). The ankle COF migrated significantly toward the medial (P = .001) and posterior (P = .023) directions. In the "mild sprain with increasing ligamentous incompetence" condition, the ankle (P = .018) and subtalar (medial facet, P = .022) peak pressure increased significantly with intact ligaments and with all ligaments cut. The ankle COF migrated significantly toward the medial direction when the ATFL and CFL or when all 3 ligaments were severed. The anteroposterior ankle COF migration was anterior when all ligaments were intact or when only the ATFL was severed but posterior when the CFL or when the CFL and the LTCL were severed in addition., Conclusion: Next to chronic inhomogeneous load distribution in the unstable hindfoot and shear stress during sprains, intra-articular pressure elevation (impact) in the ankle and subtalar joint during hindfoot supination sprains with intact ligaments or incompetent ligaments likely contributes to OCLs of the medial talar dome and the medial subtalar facet., Clinical Relevance: Intra-articular hindfoot pressure elevation (impact) in "acute severe" and in "mild hindfoot supination sprains with increasing ligamentous incompetence" is substantial for the development of OCLs at the medial midtalar dome and the medial facet of the subtalar joint.

Background: Aim of this study was to analyse the relationship between popliteal artery aneurysm (PAA) and generalized arteriomegaly., Patients and Methods: In this consecutive serie, thirty-three patients (1 woman, mean age 69.7 +/- 9.6 years) undergoing PAA repair between 1996 and 2000 agreed to participate in a duplex screening program to assess the diameters of the infrarenal abdominal aorta, common and external iliac, common and superficial femoral and contralateral popliteal arteries as well as common carotid and brachial arteries., Results: The prevalence of arteriomegaly and aneurysmal disease, respectively, was as follows: abdominal aorta 15/33 (45.5%) and 8/33 (24.2%), common iliac artery 34/66 (51.5%) and 23/66 (34.8%), common femoral artery 55/66 (83.3%) and 7/66 (10.6%) as well as contralateral popliteal artery 7/33 (21.2%) 15/33 (45.5%). Significantly larger carotid artery diameters were found comparing PAA patients with age- and body surface adjusted healthy controls (p < 0.001). Furthermore, patients with multiple peripheral arterial aneurysms had significantly larger diameters of the brachial (p < 0.02) and external iliac (p < 0.005)., Conclusions: Our findings support the hypothesis of a diathesis for a generalized arteriomegaly with a predilection for further aneurysms of the abdominal aorta, iliac arteries, femoral and contralateral popliteal arteries in patients with PAA.

Avidity describes the binding strength of specific antibody to antigen. It was found to be low in the first phase after primary infection but then to increase over time. In addition to classic serodiagnosis of toxoplasmosis, measurement of avidity provides information making it possible to distinguish between acute and chronic infection and is of particular interest in pregnant women. In 229 women we found IgG and IgM antibodies suggestive of acute infection. A total of 188 (82%) had an avidity index > 0.3, indicating that the infection had occurred at least four months earlier. Based on this additional information, repeated testing and unnecessary anxiety can be avoided.