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We aimed to evaluate retrospectively associated anomalies and outcome in prenatal aortic arch anomalies (AAAs). We included ninety patients with aberrant right subclavian artery (ARSA), right aortic arch (RAA) with mirror image branching (RAA-mirror) or aberrant left subclavian artery (RAA-ALSA) and double aortic arch (DAA) between 2011 and 2020. In total, 19/90 (21.1%) had chromosomal anomalies, the highest rate being within the ARSA subgroup (17/46, 37%). All (13/13) of the RAA-mirror subgroup, 10/27 (37.0%) of RAA-ALSA, 13/46 (28.3%) of ARSA and 0/4 within the DAA subgroup had additional intracardiac anomaly. The rate of extracardiac anomalies was 30.7% in RAA-mirror, 28.3% in ARSA, 25.0% in DAA and 22.2% in the RAA-ALSA subgroup. A total of 42/90 (46.7%) had isolated AAAs: three (7.1%) with chromosomal anomalies, all trisomy 21 (3/26, 11.5%) within the ARSA subgroup. Out of 90, 19 (21.1%) were lost to follow-up (FU). Two (2.2%) intrauterine deaths occurred, and six (6.7%) with chromosomal anomalies terminated their pregnancy. In total, 63 (70.0%) were liveborn, 3/63 (4.8%) with severe comorbidity had compassionate care and 3/60 (5.0%) were lost to FU. The survival rate in the intention-to-treat cohort was 53/57 (93%). Forty-one (77.4%) presented with vascular ring/sling, two (4.9%) with RAA-ALSA developed symptoms and one (2.4%) needed an operation. We conclude that intervention due to vascular ring is rarely necessary. NIPT could be useful in isolated ARSA cases without higher a priori risk for trisomy 21 and after exclusion of other anomalies. [ABSTRACT FROM AUTHOR]

This case report describes the clinical presentation, imaging diagnosis and histopathological findings of multiple osseous hamartomas in the thoracolumbar vertebral column of a 3‐month‐old Rhodesian Ridgeback puppy. The dog was presented due to progressive non‐painful, non‐ambulatory upper motor neuron paraparesis. Magnetic resonance imaging revealed diffuse T2‐weighted hyperintensities in the vertebral bodies of Th12, L4, S2 and the vertebral arch of Th13, and showed irregular and hyperostotic outer borders of the cortex. The diagnosis of multiple hamartomas was confirmed by histopathology showing bone cavities containing myxoid mesenchymal material, tortuous blood vessels and lipid and cartilaginous emboli in the bone marrow. This case emphasises the importance of keeping a hamartoma in mind as cause for neurological signs, especially in young animals. [ABSTRACT FROM AUTHOR]

Background: Peripheral nerve sheath tumors (PNSTs) are a group of neoplasms originating from Schwann cells or pluripotent cell of the neural crest. Therapeutic options and prognosis are influenced by their degree of malignancy and location. Hypothesis/Objectives: Identify magnetic resonance imaging (MRI) features predictive of PNST histologic grade. Animals: Forty‐four dogs with histopathological diagnosis of spinal PNSTs and previous MRI investigation. Methods: A multicenter retrospective study including cases with (a) histopathologic diagnosis of PNST and (b) MRI studies available for review. Histologic slides were reviewed and graded by a board‐certified pathologist according to a modified French system (FNCLCC) for grading soft tissue sarcomas. The MRI studies were reviewed by 2 board‐certified radiologists blinded to the grade of the tumor and the final decision on the imaging characteristics was reached by consensus. Relationships between tumor grade and histological and MRI findings were assessed using statistical analysis. Results: Forty‐four cases met inclusion criteria; 16 patients were PNSTs Grade 1 (low‐grade), 19 were PNSTs Grade 2 (medium‐grade), and 9 were PNSTs Grade 3 (high‐grade). Large volume (P =.03) and severe peripheral contrast enhancement (P =.04) were significantly associated with high tumor grade. Degree of muscle atrophy, heterogeneous signal and tumor growth into the vertebral canal were not associated with grade. Conclusions and Clinical Importance: Grade of malignancy was difficult to identify based on diagnostic imaging alone. However, some MRI features were predictive of high‐grade PNSTs including tumor size and peripheral contrast enhancement. [ABSTRACT FROM AUTHOR]

Background: Cardiomyopathies (CMs) are a heterogeneous and severe group of diseases that shows a highly variable cardiac phenotype and an incidence of app. 1/100.000. Genetic screening of family members is not yet performed routinely. Patients and methods: Three families with dilated cardiomyopathy (DCM) and pathogenic variants in the troponin T2, Cardiac Type (TNNT2) gene were included. Pedigrees and clinical data of the patients were collected. The reported variants in the TNNT2 gene showed a high penetrance and a poor outcome, with 8 of 16 patients dying or receiving heart transplantation. The age of onset varied from the neonatal period to the age of 52. Acute heart failure and severe decompensation developed within a short period in some patients. Conclusion: Family screening of patients with DCM improves risk assessment, especially for individuals who are currently asymptomatic. Screening contributes to improved treatment by enabling practitioners to set appropriate control intervals and quickly begin interventional measures, such as heart failure medication or, in selected cases, pulmonary artery banding. [ABSTRACT FROM AUTHOR]

Recent work identified anti‐GM2 and anti‐GalNAc‐GD1a IgG ganglioside antibodies as biomarkers in dogs clinically diagnosed with acute canine polyradiculoneuritis, in turn considered a canine equivalent of Guillain‐Barré syndrome. This study aims to investigate the serum prevalence of similar antibodies in cats clinically diagnosed with immune‐mediated polyneuropathies. The sera from 41 cats clinically diagnosed with immune‐mediated polyneuropathies (IPN), 9 cats with other neurological or neuromuscular disorders (ONM) and 46 neurologically normal cats (CTRL) were examined for the presence of IgG antibodies against glycolipids GM1, GM2, GD1a, GD1b, GalNAc‐GD1a, GA1, SGPG, LM1, galactocerebroside and sulphatide. A total of 29/41 IPN‐cats had either anti‐GM2 or anti‐GalNAc‐GD1a IgG antibodies, with 24/29 cats having both. Direct comparison of anti‐GM2 (sensitivity: 70.7%; specificity: 78.2%) and anti‐GalNAc‐GD1a (sensitivity: 70.7%; specificity: 70.9%) antibodies narrowly showed anti‐GM2 IgG antibodies to be the better marker for identifying IPN‐cats when compared to the combined ONM and CTRL groups (P =.049). Anti‐GA1 and/or anti‐sulphatide IgG antibodies were ubiquitously present across all sample groups, whereas antibodies against GM1, GD1a, GD1b, SGPG, LM1 and galactocerebroside were overall only rarely observed. Anti‐GM2 and anti‐GalNAc‐GD1a IgG antibodies may serve as serum biomarkers for immune‐mediated polyneuropathies in cats, as previously observed in dogs and humans. [ABSTRACT FROM AUTHOR]

The synthesis of the unsymmetric macrocyclic tetrakismidazolium salts H4‐4(PF6)4 and H4‐5(PF6)4 featuring a 2,6‐pyridinylene‐ and a 2‐bromo‐1,3‐xylylene‐bridged bisimidazolium unit is described. Reaction of macrocycle H4‐4(PF6)4 with Ag2O yields the tetranuclear complex [6](PF6)4 composed of four AgI ions sandwiched in between two tetra‐NHC ligands. The 2,6‐pyridinylene‐bridged bisimidazolium moiety of the macrocycles can be site‐selectively deprotonated and metallated with RuII or RhI to give the pincer complexes [8](PF6)3‐[11](PF6)3. Introduction of a second metal in these complexes by deprotonation/metallation and oxidative addition to the 2‐bromo‐1,3‐xylylene‐bridged bisimidazolium moiety of the macrocycles proved not possible. [ABSTRACT FROM AUTHOR]

We investigated two litters of distantly related Nova Scotia Duck Tolling Retrievers (NSDTR), of which four puppies were affected by cerebellar signs with or without neuromuscular weakness. The phenotype was termed cerebellar degeneration—myositis complex (CDMC). We suspected a heritable condition and initiated a genetic analysis. The genome of one affected dog was sequenced and compared to 565 control genomes. This search yielded a private protein-changing SLC25A12 variant in the affected dog, XM_038584842.1:c.1337C>T, predicted to result in the amino acid change XP_038440770.1:(p.Pro446Leu). The genotypes at the variant co-segregated with the phenotype as expected for a monogenic autosomal recessive mode of inheritance in both litters. Genotyping of 533 additional NSDTR revealed variant allele frequencies of 3.6% and 1.3% in a European and a North American cohort, respectively. The available clinical and biochemical data, together with current knowledge about SLC25A12 variants and their functional impact in humans, mice, and dogs, suggest the p.Pro446Leu variant is a candidate causative defect for the observed phenotype in the affected dogs. [ABSTRACT FROM AUTHOR]

A rockfall dataset for Germany is analysed with the objective of identifying the meteorological and hydrological (pre-)conditions that change the probability for such events in central Europe. The factors investigated in the analysis are precipitation amount and intensity, freeze–thaw cycles, and subsurface moisture. As there is no suitable observational dataset for all relevant subsurface moisture types (e.g. water in rock pores and cleft water) available, simulated soil moisture and a proxy for pore water are tested as substitutes. The potential triggering factors were analysed both for the day of the event and for the days leading up to it. A logistic regression model was built, which considers individual potential triggering factors and their interactions. It is found that the most important factor influencing rockfall probability in the research area is the precipitation amount at the day of the event, but the water content of the ground on that day and freeze–thaw cycles in the days prior to the event also influence the hazard probability. Comparing simulated soil moisture and the pore-water proxy as predictors for rockfall reveals that the proxy, calculated as accumulated precipitation minus potential evaporation, performs slightly better in the statistical model. Using the statistical model, the effects of meteorological conditions on rockfall probability in German low mountain ranges can be quantified. The model suggests that precipitation is most efficient when the pore-water content of the ground is high. An increase in daily precipitation from its local 50th percentile to its 90th percentile approximately doubles the probability for a rockfall event under median pore-water conditions. When the pore-water proxy is at its 95th percentile, the same increase in precipitation leads to a 4-fold increase in rockfall probability. The occurrence of a freeze–thaw cycle in the preceding days increases the rockfall hazard by about 50 %. The most critical combination can therefore be expected in winter and at the beginning of spring after a freeze–thaw transition, which is followed by a day with high precipitation amounts and takes place in a region preconditioned by a high level of subsurface moisture. [ABSTRACT FROM AUTHOR]

Background: Intervertebral disc extrusions in the thoracolumbar region are a common spinal neurologic disorder in dogs and usually considered a neurological emergency. Several factors, like timing of surgery, have previously been analysed in order to determine the effect on outcome and time of recovery. Most studies have investigated one defined population of dogs and the influence of a single factor on the overall outcome. In this retrospective study, a large cohort of dogs and the influence of one or combinations of several factors on outcome and time of recovery were analysed. Results: The bivariate analysis demonstrated a significant association between the following variables and the time of recovery: the time span between the onset of clinical signs and surgery (Cramers Phi φ ′ = 0.14; P = 0.003), the grade of severity ( φ ′ = 0.23; P < 0.001) and the implementation of physical rehabilitation ( φ ′ = 0.2; P < 0.001). However, the analysis of a multivariable regression model demonstrated that a significant correlation only exists between the time span between the onset of clinical signs and surgery and the overall outcome (P = 0.007), as well as between the grade of severity and the time of recovery (P < 0.001). The percentage of dogs with lacking deep pain perception (DPP) that had to be euthanised due to their neurological condition, decreased from 20.0 to 2.9% when physical rehabilitation was implemented. Additionally, the proportion of dogs (same group) that improved to reach an ambulatory status increased from 80.0 to 91.4%. Conclusion: The results of the bivariate analysis demonstrated several correlations between some variables and overall outcome or time of recovery, whereas the multivariable regression model demonstrated only two associations. The time span between the onset of clinical signs and surgery was significantly associated with the overall outcome. We therefore suggest that a surgical intervention should be performed without unreasonable delay. Due to the correlation between the grade of severity and time of recovery, owners of dogs with more severe neurological deficits prior to surgery should be informed about the presumably prolonged time of recovery. [ABSTRACT FROM AUTHOR]

A rockfall dataset for Germany is analysed with the objective of identifying the meteorological and hydrological (pre-) conditions that change the probability for such events in Central Europe. The factors investigated in the analysis are precipitation amount and intensity, freeze-thawing cycles as well as sub-surface moisture. As there is no suitable observational dataset for all relevant sub-surface moisture types (e.g. water in rock pores and cleft water) available, simulated soil moisture and parameterised pore water are tested as substitutes. The potential triggering factors were analysed both for the day of the event as well as for the days leading up to the event. It is found that the most important factor influencing rockfall probability in the research area is precipitation amount at the day of the event but the water content of the ground on that day and freeze-thawing cycles in the days prior to the event also influence the hazard probability. Comparing results with simulated soil moisture and parameterised pore water revealed that precipitation minus potential evaporation evaluated for a weekly period performs well as a proxy for the relevant sub-surface moisture types. A logistic regression model was built, which considers individual potential triggering factors as well as their interactions. Using this model the effects of meteorological conditions on rockfall probability in the Central European low mountain ranges can be quantified. The model suggests that precipitation is most efficient, when the moisture content of the ground is high. An increase of daily precipitation from its local 50th percentile to its 90th percentile approximately doubles the probability for a rockfall event under median sub-surface moisture conditions. When the moisture content of the ground is at its 95th percentile the same increase in precipitation leads to a four-fold increase in rockfall probability. The occurrence of a freeze-thaw cycle in the preceding days can further increase the rockfall hazard. The most critical combination can be expected in the winter season after a freeze-thaw transition which is followed by a day with high precipitation amounts and takes place in a region preconditioned by a high level of sub-surface moisture. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) often leads to heart failure. Mutations in sarcomeric proteins are most frequently the cause of HCM but in many patients the gene defect is not known. Here we report on a young man who was diagnosed with HCM shortly after birth. Whole exome sequencing revealed a mutation in the FLNC gene (c.7289C > T; p.Ala2430Val) that was previously shown to cause aggregation of the mutant protein in transfected cells. Myocardial tissue from patients with this mutation has not been analyzed before and thus, the underlying etiology is not well understood. Myocardial tissue of our patient obtained during myectomy at the age of 23 years was analyzed in detail by histochemistry, immunofluorescence staining, electron microscopy and western blot analysis. Cardiac histology showed a pathology typical for myofibrillar myopathy with myofibril disarray and abnormal protein aggregates containing BAG3, desmin, HSPB5 and filamin C. Analysis of sarcomeric and intercalated disc proteins showed focally reduced expression of the gap junction protein connexin43 and Xin-positive sarcomeric lesions in the cardiomyocytes of our patient. In addition, autophagy pathways were altered with upregulation of LC3-II, WIPI1 and HSPB5, 6, 7 and 8. We conclude that the p.Ala2430Val mutation in FLNC most probably is associated with HCM characterized by abnormal intercalated discs, disarray of myofibrils and aggregates containing Z-disc proteins similar to myofibrillar myopathy, which supports the pathological effect of the mutation. [ABSTRACT FROM AUTHOR]

This study presents an evaluation of a comprehensive dataset with information on about 700 recorded rockfall events in Germany for the first time. The focus is on the analysis of monthly distributions of three rockfall clusters in German low mountain ranges and of three elevation classes to provide an overview of the characteristic seasonal occurrence of rockfalls in Germany. Each rockfall distribution is correlated with records of meteorological station clusters which are representative for the long‐term climate conditions of the particular rockfall cluster and elevation class, respectively. The stored parameters in the dataset (year of occurrence, rock volumes, slope angles, affected objects) are evaluated to complete the extensive and differentiated overview of rockfalls in Germany. The analyses of the distributions of the three rockfall clusters show a distinct event concentration in the winter months. Differences are apparent between the monthly distributions of the elevation classes in which clear peaks are partially visible. Freeze–thaw cycles are considered to be the major trigger of winter rockfalls in Germany. Overall, the presented results may serve as a basis for further studies in the German low mountain ranges. © 2020 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Previous investigations assessing the genetic cause of pediatric hypertrophic cardiomyopathy (HCM) found underlying genetic mutations in 50-60% of cases. The purpose of our study was to analyze whether this number can be augmented by applying next-generation sequencing and directing further diagnostics by discussing unsolved cases in a multidisciplinary board.Methods and results: 42 patients with the diagnoses of HCM made before age 18 years were treated in our center from 2000 to 2016. Genetic analysis was performed in 36 subjects, a genetic defect was detected in 29 (78%) patients. 15 individuals (42%) had pathogenic variants in genes encoding sarcomere proteins, and 5 (14%) in genes coding for components of the RAS/MAPK signaling pathway. 4 subjects (11%) had mutations in the GAA gene (Pompe disease), and 3 (8%) had Frataxin repeat expansions (Friedreich's ataxia). One patient each showed a mutation in BAG3 and LMNA. Discussion of unsolved HCM cases after performing next-generation sequencing (28 genes) in an interdisciplinary board unraveled the genetic cause in 9 subjects (25%).Conclusion: A definite genetic diagnosis can be reached in nearly 80% with HCM of childhood onset. Next-generation sequencing in conjunction with a multidisciplinary cooperation can enhance the diagnostic yield substantially. This may be important for risk stratification, treatment planning and genetic counseling. [ABSTRACT FROM AUTHOR]

While in adults major advances in heart failure therapy in patients with dilated cardiomyopathy were documented in the last two decades, research on the mechanism and therapies of heart failure in children with left ventricular dilated cardiomyopathy has lagged behind. Despite the lack of sufficient randomized prospective studies, ACE inhibitors are first line and ß-receptor antagonists are second-line strategies in children. Following the adult guidelines, without having data concerning the pediatric population, mineral corticoids are also accepted in the treatment of pediatric heart failure, while diuretics should only be used to achieve a euvolemic status. In cases of complete left bundle bunch block or prolonged QRS duration, cardiac resynchronization is an option. If these instruments are exploited, and the child is still listed for heart transplantation as destination, evolving therapies like pulmonary artery banding in cases of preserved right ventricular function and cardiac cell therapy in cases of localized ventricular dysfunction might represent additional treatment options. This review summarizes the actual guidelines and provides an outlook for evolving therapies. [ABSTRACT FROM AUTHOR]

Very young mammals have an impressive cardiac regeneration capacity. In contrast, cardiac regeneration is very limited in adult humans. The hearts of young children have a higher regenerative capacity compared with adults, as, for example, seen after surgical correction of an anomalous left coronary artery arising from the pulmonary artery or in children with univentricular hearts, who present enormous morphological changes after volume unloading. In addition, the enormous regenerative potential of growing children's hearts is reflected in the spontaneous courses of children with severely deteriorated cardiac function (e.g., patients with dilated cardiomyopathy). The extent of this regenerative capacity and its time dependency remain to be elucidated in the future and should be exploited to improve the treatment of children with severe heart insufficiency. [ABSTRACT FROM AUTHOR]

Pulmonary arterial endothelial function is known to be affected in patients with idiopathic pulmonary arterial hypertension (IPAH). Current reports also detected peripheral systemic arterial dysfunction in IPAH patients. The purpose of this study was to assess whether there is a relation between pulmonary arterial and systemic arterial endothelial function. Pulmonary arterial endothelium-dependent relaxation was assessed by changes in pulmonary blood flow in response to acetylcholine which were determined using intravascular Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to acetylcholine relative to baseline values. Systemic arterial endothelial function was assessed by the vascular response to reactive hyperemia, and was recorded non-invasively by peripheral arterial finger tonometry under standardized conditions. Thirteen children and young adults [mean age 16.7 (±5.6) years] with IPAH and 13 age-/gender-matched controls were included in the study. Digital reactive hyperemic index (RHI) of the IPAH patients was 1.54 (±0.69), and of the controls was 1.67 (±0.66) [ p = 0.64]. The mean baseline flow velocity in the segmental pulmonary artery of all patients was 18.5 (±5.5) cm/s, increasing to 27.4 (±12.3) cm/s ( p = 0.003) during acetylcholine infusion. The calculated mean PFR was 1.48 (±0.4). There was no significant correlation between the PFR and RHI ( r = 0.19; p = 0.54). According to our results, systemic arterial endothelial function assessed by peripheral arterial finger tonometry was not significantly impaired in children and young adults with IPAH compared with age-/gender-matched controls. There was no correlation between systemic arterial and pulmonary arterial endothelial function, suggesting that different mechanisms may contribute to their pathogenesis and progression. [ABSTRACT FROM AUTHOR]

Background In patients with anomalous left coronary artery from the pulmonary artery (ALCAPA) left ventricular (LV) dilatation and dysfunction evolves due to diminished myocardial perfusion caused by coronary steal phenomenon. Using late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) imaging, myocardial scarring has been shown in ALCAPA patients late after repair, however the incidence of scarring before surgery and its impact on postoperative course after surgical repair remained unknown. Methods 8 ALCAPA-patients (mean age 10.0 ± 5.8 months) underwent CMR before and early after (mean 4.9 ± 2.5 months) coronary reimplantation procedures. CMR included functional analysis and LGE for detection of myocardial scars. Results LV dilatation (mean LVEDVI 171 ± 94 ml/m2) and dysfunction (mean LV-EF 22 ± 10 %) was present in all patients and improved significantly after surgery (mean LVEDV 68 ± 42 ml/m2, p = 0.02; mean LV-EF 58 ± 19 %, p < 0.001). Preoperative CMR revealed myocardial scarring in 2 of the 8 patients and did not predict postoperative course. At follow-up CMR, one LGE-positive patient showed delayed recovery of LV function while myocardial scarring was still present in both patients. In two patients new-onset transmural scarring was found, although functional recovery after operation was sufficient. One of them showed a stenosis of the left coronary artery and required resurgery. Conclusions Despite diminished myocardial perfusion and severely compromised LV function, myocardial scarring was preoperatively only infrequently present. Improvement of myocardial function was independent of new-onset scarring while the impact of preoperative scarring still needs to be defined. [ABSTRACT FROM AUTHOR]

Preservation of the pulmonary valve, even at the expense of a mild residual stenosis, is the current surgical policy for the management of patients with tetralogy of Fallot (TOF). This study aimed to assess the long-term effect of a residual right ventricular outflow tract obstruction (RVOTO) on RV dimension and function. This study prospectively assessed 53 children (mean age, 13.4 ± 6.4 years) after repair of TOF using cardiovascular magnetic resonance imaging. Residual RVOTO on echocardiography was defined as a peak systolic RVOT gradient of 25 mmHg or higher. Patients with RVOTO ( n = 29) had significantly less pulmonary regurgitation (25.2 ± 10.6 %) than patients without RVOTO (30.8 ± 9.3 %; p = 0.05) ( n = 24). Compared with patients who had no RVOTO, children with RVOTO had significantly smaller RV end-diastolic volume (94.0 ± 2.6 vs 104.0 ± 20.7 ml/m; p < 0.05) and end-systolic volume (42.9 ± 20.0 vs 48.9 ± 13.2 ml/m; p < 0.05), whereas RV ejection fraction did not differ significantly between the two groups (55.5 ± 8.4 vs 54.0 ± 6.6 %). Restrictive physiology, assessed by late diastolic forward flow in the main pulmonary artery, was equally distributed within the two groups (31 vs 25 %; nonsignificant difference). According to the study data, residual RVOTO after repair of TOF does not affect RV function, whereas RV dimensions and the degree of pulmonary regurgitation are more favorable in the long-term follow-up evaluation of those patients. These results confirm the beneficial effects of the current strategy for repair of TOF. [ABSTRACT FROM AUTHOR]

Recent studies suggest that the mammalian heart possesses some capacity for cardiac regeneration. This regenerative capacity is primarily documented postnatally and after myocardial infarction or pressure overload. Although the cell type that mediates endogenous regeneration is unclear, cardiac stem cells might be considered as potential candidates. To determine the number of c-kit + cardiac resident cells under conditions of pressure overload, we evaluated specimens derived from n = 8 patients with pressure overloaded single right ventricles in comparison to n = 4 explanted hearts from patients with dilated cardiomyopathy and n = 14 biopsies from children after heart transplantation. The age of the patients ranged from 16 days to 19 years. For quantification of cardiac stem cells, c-kit+/mast cell tryptase-/CD45- cells were counted and expressed as percent of the total nuclei. In specimens from patients with dilated cardiomyopathy, 0.13 ± 0.09% c-kit +/mast cell tryptase-/CD45- cells were detected. However, in specimens from patients with pressure overloaded single right ventricles, the numbers of c-kit+/mast cell tryptase-/CD45- cells were significantly higher (0.41 ±0.24%, p < 0.05). Under conditions of pressure overload, the right ventricle shows an approximately three-fold increase in c-kit+/mast cell tryptase-/CD45- cardiac resident cells. Despite the fact that this increased number of c-kit+ cells is not sufficient to prevent the failing heart from congestive heart failure, understanding the mechanism that leads to an increase of presumably cardiac resident stem cells under conditions of pressure overload might help to develop new strategies to enhance endogenous repair. [ABSTRACT FROM AUTHOR]

Aims The identification of factors that mobilize subsets of endogenous progenitor cells may provide new therapeutic tools to enhance the repair of ischaemic tissue. We previously identified circulating mesenchymal cells that co-express endothelial markers (so-called circulating mesoangioblasts, cMABs) in children undergoing heart surgery with cardiopulmonary bypass (CPB). However, the mechanisms by which these cells are mobilized and their origin is unclear. Methods and results Circulating CD73+CD45−KDR+ cMABs were analysed in adults undergoing heart surgery with (n = 21) or without CPB (n = 8). During surgery with CPB, cMABs are mobilized with a maximal response at the end of the operation. In contrast, off-pump heart surgery does not stimulate cMAB mobilization, indicating that the stress mediated by CPB induces the mobilization of cMAB. Circulating mesoangioblasts were enriched in blood obtained from the coronary sinus. Histologically, CD73+ cells were detected around vessels in the heart, indicating that the heart is one of the niches of cMABs. Consistently, studies in gender mismatched bone marrow transplanted patients demonstrated that cMABs did not originate from the bone marrow. Cytokine profiling of serum samples revealed that hepatocyte growth factor (HGF) was profoundly increased at the time point of maximal mobilization of cMABs. Hepatocyte growth factor stimulated the migration of cMABs. Importantly, injection of recombinant HGF increased cMABs in rats. Conclusions Hepatocyte growth factor induces mobilization of non-haematopoietic progenitor cells with a cardiac repair capacity. This newly identified function together with the known pleiotrophic effects of HGF makes HGF an attractive therapeutic option for the treatment of ischaemic heart disease. [ABSTRACT FROM PUBLISHER]

Aims: Left ventricular non-compaction (LVNC) is caused by mutations in multiple genes. It is still unclear whether LVNC is the primary determinant of cardiomyopathy or rather a secondary phenomenon with intrinsic cardiomyocyte dysfunction being the actual cause of the disease. Here, we describe a family with LVNC due to a novel missense mutation, pE96K, in the cardiac troponin T gene (TNNT2). [ABSTRACT FROM PUBLISHER]

DCM is the most common cardiomyopathy in childhood. Effectiveness of anticongestive therapy is limited in most cases and about one-third of children diagnosed with DCM die or receive heart transplantation within the first year after diagnosis. Cardiac stem cell transplantation has become a promising therapy to treat heart failure in adult patients. Based on these promising results, the cardiac stem cell therapy might also represent a new therapeutic option particularly in young children. The present case documents for the first time intracoronary administration of autologous bone marrow-derived progenitor cells in a critically ill two-yr-old child with severe heart failure caused by DCM. Because of progressive worsening of the clinical condition despite maximal anticongestive treatment, the decision to perform autologous stem cell therapy was made. Cardiac stem cell therapy proved to be technically feasible, was associated with improvement in cardiac function, and might represent an option before heart transplantation in children with severe heart failure. [ABSTRACT FROM AUTHOR]

Extracorporeal shock wave lithotripsy (ESWL) has been used increasingly in clinical practice over the last few years. The aim of this study was to investigate the effects of shock waves on cartilage often unintentionally placed inside the focal volume during ESWL. We investigated whether the physical state of the chondrocytes exposed to shock waves has an influence on cell lethality. Chondrocytes of 12 patients were exposed to shock waves generated by a Piezoson 300. We used 200 shock waves of different energy levels (0.08 and 0.26 mJ/mm2) and the cells were prepared in two physical states: a fluid suspension and a viscous alginate. After ESWL the percentage of dead cells was determined by microscopy. DNA electrophoresis was carried out to detect fragmentation of the DNA. A significant increase of dead cells at higher energy levels in suspension ( P = 0.001) in contrast to alginate medium ( P = 0.263) was detected immediately after ESWL. The long-term survival of chondrocytes was not affected in either substance, as shown in an investigation of the cells three weeks after ESWL. At the molecular level a permeabilisation of the cell membrane was detected. DNA was not affected, even at high-energy levels. Alginate is definitely closer to the real state of cartilage in vivo than suspension. Therefore the negative effects of shock waves which are shown in many investigations that used cells in suspension are not necessarily to be expected in vivo. It can be assumed that side effects will not occur in a clinical setting. [ABSTRACT FROM AUTHOR]

To perform an open-wedge high-tibial osteotomy (HTO), the medial proximal tibia is frequently exposed by partial distal release of the overlying insertion of the medial collateral ligament (MCL). Biomechanically, any release of the MCL can increase knee laxity when valgus stress is applied. Clinically however, post-surgical valgus instability following HTO with partial MCL release is an uncommon complication. It is known that the open-wedge procedure can re-tention an intact MCL by the width of the base of the wedge. However, this re-tentioning effect is uncertain in small wedge sizes, preexisting medial compartment laxity and in the presence of a partially detached MCL. Considering the good clinical results after HTO, we hypothesized that a partial release of the superficial MCL for HTO does not play a crucial role in stabilizing valgus forces in the human knee. We therefore measured the effect of partial versus complete release of the superficial MCL to determine medial knee laxity represented by the amount of medial joint opening (MJO) under valgus stress in this human cadaver study. In ten knee pairs, the superficial and deep MCL were sectioned in sequence with a standardized abduction force of 15 kp with a Scheuba apparatus applied. In group 1 (5 knee pairs), the superficial MCL was completely sectioned whereas in group 2 (5 knee pairs), sectioning of the superficial MCL was restricted to the anterior border to mimic the surgical exposure for an HTO. To account for the interindividual variability of ligamentous laxity, only increments of MJO within knee pairs were statistically evaluated. Stress radiography did not reveal any significant differences in increments of MJO between knee pair specimens with complete versus partial release of the superficial MCL. We disproved our hypothesis and concluded that the anterior fibers of the superficial MCL do play a crucial role in maintaining valgus stability in this biomechanical setting. Therefore, the release of the superficial MCL for open-wedge HTO should be kept to a minimum to decrease the potential of late valgus instability. This is especially important in patients with small wedge sizes and medial compartment laxity since the anterior MCL fibers are the main contributor to medial joint stability and the re-tentioning effect of the remaining MCL fibers is presumably decreased. [ABSTRACT FROM AUTHOR]

Abstract: Progenitor cells may contribute to cardiac regeneration. Here, we investigated the role of cadherins and integrins for differentiation of human adult circulating endothelial progenitor cells (EPCs) into cardiomyocytes (CM) in a co-culture system. N- and E-cadherin were expressed in EPCs and were localized at the interface between EPCs and CM. Incubation of a blocking antibody against E-cadherin reduced the expression of CM marker protein in EPCs. Blocking antibodies against N- or P-cadherin or the β1- and β2-integrins were not effective. These data suggested that cell-to-cell communication mediated by E-cadherin contributes to the acquirement of a cardiomyogenic phenotype of human endothelial progenitor cells. [Copyright &y& Elsevier]

Introduction The aim of this study was to investigate the effect of extracorporeal shock wave therapy (ESWT) on the ultrasonographic appearance of chronically painful, proximal plantar fasciitis. Materials and methods Twenty-two patients with a unilateral proximal plantar fasciitis were prospectively enrolled after unsuccessful conservative treatment lasting 6 months. The contralateral plantar fascia was used as the control. ESWT (3·3000 shock waves/session of 0.2 mJ/mm2) was performed at weekly intervals. The thickness of the plantar fascia was measured ultrasonographically about 2 cm distal of the medial calcaneal tuberosity. Pain estimation on a visual analogue scale (VAS) and the comfortable walking time were recorded. No local anaesthesia was applied. Follow-up was done at 6, 12 and 24 weeks. Results Before ESWT, the plantar fasciitis side was ultrasonographically significantly thicker than the control side (p<0.05), whereas 6 months after ESWT, the thickness of the fascia was no longer significantly different. The decrease in thickness of the plantar fasciitis side was significant (p<0.05). Pain during activities of daily living decreased by 79% according to the VAS, and the comfortable walking time increased, both significantly (p<0.01). In patients with little pain (VAS<30), the thickness of the plantar fasciitis side was significantly less (p<0.01) compared with patients who still suffered more pain (VAS>30). Conclusion After ESWT, the thickness of the plantar fascia in patients with plantar fasciitis decreased, pain and walking time improved (all significantly). [ABSTRACT FROM AUTHOR]

Human endothelial progenitor cells (EPCs) can differentiate into cardiomyogenic cells in vitro. We tested the effects of statin therapy on the differentiation rate of EPCs from patients with coronary artery disease (CAD), who may benefit from autologous cell therapy. EPCs from 3 age-matched groups were tested: No CAD (n = 13), CAD patients with (n = 10) or without (n = 16) statin therapy. From 4 CAD patients, EPCs were tested before and after 4 weeks of therapy with 20 mg atorvastatin. After 6 days of co-culture with rat neonatal cardiomyocytes, EPC differentiation was quantified by immunostaining for α-sarcomeric actinin flow cytometry analysis. After 6 days of co-culture, the percentage of -sarcomeric actinin–positive EPCs was significantly (p = 0.014) higher in EPCs from adults without CAD (8.07% ± 1.48% of EPCs) compared to EPCs from CAD patients without statin (3.56% ± 0.72%). Importantly, patients with statin therapy revealed significantly higher numbers of α-sarcomeric actinin-positive EPCs (6.36% ± 0.69%, p = 0.01) compared to CAD patients without statin. In addition, statin therapy resulted in a significant (p = 0.017) increase of EPC differentiation in all 4 CAD patients investigated before and 4 weeks after statin therapy. The survival of EPCs did not differ between the different groups suggesting that the regulation of EPC differentiation is not secondary to altered EPC survival. In vitro, EPC treatment with 0.1 µM atorvastatin did not affect EPC differentiation (116.15% ± 49.11% of control). EPCs from patients with CAD display impaired differentiation into cardiomyogenic cells. This defect can be improved by in vivo, statin therapy. [ABSTRACT FROM AUTHOR]

Background: Reliable fixation of the soft hamstring grafts in ACL reconstruction has been reported as problematic. Hypothesis: The biomechanical properties of patellar tendon (PT) grafts fixed with biodegradable screws (PTBS) are superior compared to quadrupled hamstring grafts fixed with BioScrew (HBS) or Suture-Disc fixation (HSD). Study Design: Controlled laboratory study with roentgen stereometric analysis (RSA). Methods: Ten porcine specimens were prepared for each group. In the PT group, the bone plugs were fixed with a 7 × 25 mm BioScrew. In the hamstring group, four-stranded tendon grafts were anchored within a tibial tunnel of 8 mm diameter either with a 7 × 25 mm BioScrew or eight polyester sutures knotted over a Suture-Disc. The grafts were loaded stepwise, and micromotion of the graft inside the tibial tunnel was measured with RSA. Results: Hamstring grafts failed at lower loads (HBS: 536 N, HSD 445 N) than the PTBS grafts (658 N). Stiffness in the PTBS group was much greater compared to the hamstring groups (3500 N/mm versus HBS = 517 N/mm and HSD = 111 N/mm). Irreversible graft motion after graft loading with 200 N was measured at 0.03 mm (PTBS), 0.38mm (HBS), and 1.85mm (HSD). Elasticity for the HSD fixation was measured at 0.67 mm at 100 N and 1.32 mm at 200 N load. Conclusion: Hamstring graft fixation with BioScrew and Suture-Disc displayed less stiffness and early graft motion compared to PTBS fixation. Screw fixation of tendon grafts is superior to Suture-Disc fixation with linkage material since it offers greater stiffness and less graft motion inside the tibial tunnel. Clinical Relevance: Our results revealed graft motion for hamstring fixation with screw or linkage material at loads that occur during rehabilitation. This, in turn, may lead to graft laxity. [ABSTRACT FROM AUTHOR]

Presents several letters addressed to the editor regarding topics and issues related to sports medicine. Partial-thickness rotator cuff tear; Fatigue testing of orthopaedic fixation devices; Tendon abnormalities in athletes.

Reports on three cases of chondral lesions that occurred in patients after the repair of meniscal tears with bioabsorbable implants. Clinical profile of the patients; Advantages of meniscal repair with bioabsorbable implants; Ways to avoid chondral damage from bioabsorbable implants.

Aseptic osteonecrosis of the medial femoral condyle has recently been reported as a complication of arthroscopic surgery. The time interval between the onset of symptoms and pathognomonic MRI changes (diagnostic window) is not known for osteonecrosis of the knee. To determine the prevalence of early-stage spontaneous osteonecrosis of the knee (SONK) we prospectively examined 176 patients by MRI between May 1998 and December 1999. In six patients MRI revealed a bone marrow edema pattern and subtle subchondral bone changes in the medial condyle consistent with early-stage SONK (prevalence of 3.4%); in the 53 patients older than 65 years the prevalence was 9.4%. In 10 patients (5.7%) the bone and marrow changes on MRI imaging either resolved on follow-up MRI and were regarded as transient epiphyseal lesions or were considered to be reactive changes due to underlying degenerative articular disease. Including MRI in the preoperative diagnostic procedures could avoid missing the diagnosis of avascular necrosis before planning an operative treatment of suspected meniscal tears in elderly patients. [ABSTRACT FROM AUTHOR]

Presents a study that subjected anchor-suture constructs to a fatigue-testing protocol that determined the relationship between load and probability of failure. Components and interfaces of soft tissue fixation to bone; Application of single pull to failure and fatigue testing; Fatigue testing of anchors threaded with sutures.

Provides information on a study that determined the prevalence of popliteal cysts and the associated intraarticular lesions in a group of 100 patients scheduled for arthroscopic surgery of the knee. Methodology of the study; Results and discussion on the study; Conclusions.

Unlabelled: The objective of the study was to compare prospectively short-term and mid-term results after ACL reconstruction with special focus on changes in instrumented knee laxity. Methods: The original study group included prospectively 58 patients who underwent arthroscopically assisted ACL reconstruction with BPTB graft in a two-tunnel technique between 1991 and 1993. Seven patients were lost to follow-up, leaving 51 patients for a first follow-up at 6 months and a second follow-up at 3-6 years (mean 4.3 years). Clinical results were evaluated by means of the Lysholm score and the IKDC score. Laxity was assessed using a KT-1000 arthrometer applying an 89 N anterior load in 20 degrees of flexion. Increased laxity was defined as a 3 mm increase in AP translation between the first and the second follow-up. Results: At mid-term follow-up pivot shift was negative in 86% of cases. IKDC score: normal = 28%, nearly normal = 44%, abnormal = 24%, severely abnormal = 4%. KT-1000: < 3 mm = 68%, 3-5 mm = 24%, > 5 mm = 8%. The mean KT-1000 side-to-side difference was 1.08 (0.17) mm at 6 months and 2.01 (0.29) mm at 3-6 years. The difference was statistically significant (P < 0.005). According to the defined criteria, seven patients had increased laxity at the second follow-up, suggesting a malfunction of the graft due to stretch-out or injury. In this subgroup the mean KT-1000 measurements were 0.86 (0.26) mm at the first follow-up and 5.93 (0.54) mm at the second follow-up. In five of these patients, a malposition of the tunnels was identified as a possible cause. In the remaining group, KT-1000 measurements did not differ significantly between the first and the second follow-up [1.12 (0.20) mm versus 1.37 (0.21) mm]. Conclusions: Increase in AP laxity occurred in 14% of our cases between the first and the second follow-up. In most of these cases increased laxity was due to inadequate surgical technique, especially malposition of bony tunnels. If tunnel position was correct, there was no evidence for elongation of grafts over time as a general principle. [ABSTRACT FROM AUTHOR]

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The aim of this study was to evaluate the effect of extracorporal shock wave therapy (ESWT) in tennis elbow and painful heel. Nineteen patients with tennis elbow and 44 patients with painful heel in which conservative treatment had failed underwent ESWT. Both groups received 3000 shock waves of 0.12 mJ/mm2 three times at weekly intervals. After a follow-up of 5 and 6 months respectively, pain measured on a visual analogue scale (VAS) decreased significantly in both groups. The success rate (excellent and good results) was 63% in tennis elbows and 70% in painful heels. ESWT seems to be a useful conservative alternative in the treatment of both conditions. [ABSTRACT FROM AUTHOR]

Canine Lafora disease is a recessively inherited, rapidly progressing neurodegenerative disease caused by the accumulation of abnormally constructed insoluble glycogen Lafora bodies in the brain and other tissues due to the loss of NHL repeat containing E3 ubiquitin protein ligase 1 (NHLRC1). Dogs have a dodecamer repeat sequence within the NHLRC1 gene, which is prone to unstable (dynamic) expansion and loss of function. Progressive signs of Lafora disease include hypnic jerks, reflex and spontaneous myoclonus, seizures, vision loss, ataxia and decreased cognitive function. We studied five dogs (one Chihuahua, two French Bulldogs, one Griffon Bruxellois, one mixed breed) with clinical signs associated with canine Lafora disease. Identification of polyglucosan bodies (Lafora bodies) in myocytes supported diagnosis in the French Bulldogs; muscle areas close to the myotendinous junction and the myofascial union segment had the highest yield of inclusions. Postmortem examination of one of the French Bulldogs revealed brain Lafora bodies. Genetic testing for the known canine NHLRC1 mutation confirmed the presence of a homozygous mutation associated with canine Lafora disease. Our results show that Lafora disease extends beyond previous known breeds to the French Bulldog, Griffon Bruxellois and even mixed-breed dogs, emphasizing the likely species-wide nature of this genetic problem. It also establishes these breeds as animal models for the devastating human disease. Genetic testing should be used when designing breeding strategies to determine the frequency of the NHLRC1 mutation in affected breeds. Lafora diseases should be suspected in any older dog presenting with myoclonus, hypnic jerks or photoconvulsions. [ABSTRACT FROM AUTHOR]