Endomyocardial biopsy: safety and prognostic utility in paediatric and adult myocarditis in the European Society of Cardiology EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry.

BACKGROUND AND AIMS: Contemporary multicentre data on clinical and diagnostic spectrum and outcome in myocarditis are limited. Study aims were to describe baseline features, 1-year follow-up, and baseline predictors of outcome in clinically suspected or biopsy-proven myocarditis (2013 European Society of Cardiology criteria) in adult and paediatric patients from the EURObservational Research Programme Cardiomyopathy and Myocarditis Long-Term Registry. METHODS: Five hundred eighty-one (68.0% male) patients, 493 adults, median age 38 (27-52) years, and 88 children, aged 8 (3-13) years, were divided into 3 groups: Group 1 (n = 233), clinically suspected myocarditis with abnormal cardiac magnetic resonance; Group 2 (n = 222), biopsy-proven myocarditis; and Group 3 (n = 126) clinically suspected myocarditis with normal or inconclusive or no cardiac magnetic resonance. Baseline features were analysed overall, in adults vs. children, and among groups. One-year outcome events included death/heart transplantation, ventricular assist device (VAD) or implantable cardioverter defibrillator (ICD) implantation, and hospitalization for cardiac causes. RESULTS: Endomyocardial biopsy, mainly right ventricular, had a similarly low complication rate in children and adults (4.7% vs. 4.9%, P = NS), with no procedure-related death. A classical myocarditis pattern on cardiac magnetic resonance was found in 31.3% of children and in 57.9% of adults with biopsy-proven myocarditis (P < .001). At 1-year follow-up, 11/410 patients (2.7%) died, 7 (1.7%) received a heart transplant, 3 underwent VAD (0.7%), and 16 (3.9%) underwent ICD implantation. Independent predictors at diagnosis of death or heart transplantation or hospitalization or VAD implantation or ICD implantation at 1-year follow-up were lower left ventricular ejection fraction and the need for immunosuppressants for new myocarditis diagnosis refractory to non-aetiology-driven therapy. CONCLUSIONS: Endomyocardial biopsy was safe, and cardiac magnetic resonance using Lake Louise criteria was less sensitive, particularly in children. Virus-negative lymphocytic myocarditis was predominant both in children and adults, and use of immunosuppressive treatments was low. Lower left ventricular ejection fraction and the need for immunosuppressants at diagnosis were independent predictors of unfavourable outcome events at 1 year.

Infraorbital canal variants and its clinical and surgical implications. A systematic review.

BACKGROUND: Recent literature highlights anomalous cranial nerves in the sinonasal region, notably in the sphenoid and maxillary sinuses, linked to anatomical factors. However, data on the suspended infraorbital canal (IOC) variant is scarce in cross-sectional imaging. Anatomical variations in the sphenoid sinuses, including optic, maxillary, and vidian nerves, raise interest among specialists involved in advanced sinonasal procedures. The infraorbital nerve's (ION) course along the orbital floor and its abnormal positioning within the orbital and maxillary sinus region pose risks of iatrogenic complications. A comprehensive radiological assessment is crucial before sinonasal surgeries. Cone-beam computed tomography (CBCT) is preferred for its spatial resolution and reduced radiation exposure. OBJECTIVE: The aim of this study was to describe the prevalence of anatomical variants of the infraorbital canal (IOC) and report its association with clinical condition or surgical implication. METHODS: We searched Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS databases from their inception up to June 2023. Two authors independently performed the search, study selection, data extraction, and assessed the methodological quality with assurance tool for anatomical studies (AQUA). Finally, the pooled prevalence was estimated using a random effects model. RESULTS: Preliminary results show that three types are prevalent, type 1: the IOC does not bulge into the maxillary sinus (MS); therefore, the infraorbital foramen through the anterior wall of MS could be used for identification of the ION. Type 2: the IOC divided the orbital floor into medial and lateral aspects. Type 3: the IOC hangs in the MS and the entire orbital floor lying above the IOC. From which the clinical implications where mainly surgical, in type 1 the infraorbital foramen through the anterior wall of MS could be used for identification of the ION, while in type 2, since the lateral orbital floor could not be directly accessed an inferiorly transposition of ION is helpful to expose the lateral orbital wall directly with a 0 scope; or using angled endoscopes and instruments, however, the authors opinion is that direct exposure potentially facilitates the visualization and management in complex situations such as residual or recurrent mass, foreign body, and fracture located at the lateral aspect of the canal. Lastly, in type 3, the ION it's easily exposed with a 0° scope. CONCLUSIONS: This systematic review identified four IOC variants: Type 1, within or below the MS roof; Type 2, partially protruding into the sinus; Type 3, fully protruding into the sinus or suspended from the roof; and Type 4, in the orbital floor. Clinical recommendations aim to prevent nerve injuries and enhance preoperative assessments. However, the lack of consistent statistical methods limits robust associations between IOC variants and clinical outcomes. Data heterogeneity and the absence of standardized reporting impede meta-analysis. Future research should prioritize detailed reporting, objective measurements, and statistical approaches for a comprehensive understanding of IOC variants and their clinical implications. Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/UGYFZ .

Anatomy of vertebral artery hypoplasia and its relationship with clinical implications: a systematic review and meta-analysis of prevalence.

PURPOSE: The vertebral artery (VA) is a vital branch of the subclavian artery, coursing through the transverse foramina of the cervical vertebrae, and playing a crucial role in irrigating the posterior region of the arterial cerebral circle, also known as the Polygon of Willis. Among the various possible alterations that can affect the VA, vertebral artery hypoplasia (HAV) emerges as a significant variant. This study aims to discern the anatomical features of HAV and its correlation with the clinical conditions of the posterior cerebral circulation. METHODS: The databases Medline, Scopus, Web of Science, Google Scholar, CINAHL, and LILACS were searched until January 2024. Two authors independently performed the search, study selection, and data extraction. Methodological quality was evaluated with an assurance tool for anatomical studies (AQUA). Pooled prevalence was estimated using a random effects model. RESULTS: A total of 24 studies met the established selection criteria, with a total of 8847 subjects. In this study, 6 articles were included for the meta-analysis with a total of subjects. The average prevalence of VAH reported in each study was 11% (95% CI 10-12%); the studies had a heterogeneity of 41% based on the funnel plot and a low risk of bias. CONCLUSION: The prevalence of VAH is low, but in the presence of this condition, the changes are mainly in diameter rather than morphological. If it is present, some clinical safeguards must be taken to avoid complications such as stroke.

Importance of genotype for risk stratification in arrhythmogenic right ventricular cardiomyopathy using the 2019 ARVC risk calculator.

AIMS: To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: The study cohort comprised 554 patients with a definite diagnosis of ARVC and no history of sustained ventricular arrhythmia (VA). During a median follow-up of 6.0 (3.1,12.5) years, 100 patients (18%) experienced the primary VA outcome (sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator intervention, aborted sudden cardiac arrest, or sudden cardiac death) corresponding to an annual event rate of 2.6% [95% confidence interval (CI) 1.9-3.3]. Risk estimates for VA using the 2019 ARVC risk model showed reasonable discriminative ability but with overestimation of risk. The ARVC risk model was compared in four gene groups: PKP2 (n = 118, 21%); desmoplakin (DSP) (n = 79, 14%); other desmosomal (n = 59, 11%); and gene elusive (n = 160, 29%). Discrimination and calibration were highest for PKP2 and lowest for the gene-elusive group. Univariable analyses revealed the variable performance of individual clinical risk markers in the different gene groups, e.g. right ventricular dimensions and systolic function are significant risk markers in PKP2 but not in DSP patients and the opposite is true for left ventricular systolic function. CONCLUSION: The 2019 ARVC risk model performs reasonably well in gene-positive ARVC (particularly for PKP2) but is more limited in gene-elusive patients. Genotype should be included in future risk models for ARVC.

Lamin A/C Ablation Restricted to Vascular Smooth Muscle Cells, Cardiomyocytes, and Cardiac Fibroblasts Causes Cardiac and Vascular Dysfunction.

Mutations in the LMNA gene (encoding lamin A/C proteins) cause several human cardiac diseases, including dilated cardiomyopathies (LMNA-DCM). The main clinical risks in LMNA-DCM patients are sudden cardiac death and progressive left ventricular ejection fraction deterioration, and therefore most human and animal studies have sought to define the mechanisms through which LMNA mutations provoke cardiac alterations, with a particular focus on cardiomyocytes. To investigate if LMNA mutations also cause vascular alterations that might contribute to the etiopathogenesis of LMNA-DCM, we generated and characterized Lmnaflox/floxSM22αCre mice, which constitutively lack lamin A/C in vascular smooth muscle cells (VSMCs), cardiac fibroblasts, and cardiomyocytes. Like mice with whole body or cardiomyocyte-specific lamin A/C ablation, Lmnaflox/floxSM22αCre mice recapitulated the main hallmarks of human LMNA-DCM, including ventricular systolic dysfunction, cardiac conduction defects, cardiac fibrosis, and premature death. These alterations were associated with elevated expression of total and phosphorylated (active) Smad3 and cleaved (active) caspase 3 in the heart. Lmnaflox/floxSM22αCre mice also exhibited perivascular fibrosis in the coronary arteries and a switch of aortic VSMCs from the 'contractile' to the 'synthetic' phenotype. Ex vivo wire myography in isolated aortic rings revealed impaired maximum contraction capacity and an altered response to vasoconstrictor and vasodilator agents in Lmnaflox/floxSM22αCre mice. To our knowledge, our results provide the first evidence of phenotypic alterations in VSMCs that might contribute significantly to the pathophysiology of some forms of LMNA-DCM. Future work addressing the mechanisms underlying vascular defects in LMNA-DCM may open new therapeutic avenues for these diseases.

Alpha-protein kinase 3 (ALPK3) truncating variants are a cause of autosomal dominant hypertrophic cardiomyopathy.

AIMS: The aim of this study was to determine the frequency of heterozygous truncating ALPK3 variants (ALPK3tv) in patients with hypertrophic cardiomyopathy (HCM) and confirm their pathogenicity using burden testing in independent cohorts and family co-segregation studies. METHODS AND RESULTS: In a discovery cohort of 770 index patients with HCM, 12 (1.56%) were heterozygous for ALPK3tv [odds ratio(OR) 16.11, 95% confidence interval (CI) 7.94-30.02, P = 8.05e-11] compared to the Genome Aggregation Database (gnomAD) population. In a validation cohort of 2047 HCM probands, 32 (1.56%) carried heterozygous ALPK3tv (OR 16.17, 95% CI 10.31-24.87, P < 2.2e-16, compared to gnomAD). Combined logarithm of odds score in seven families with ALPK3tv was 2.99. In comparison with a cohort of genotyped patients with HCM (n = 1679) with and without pathogenic sarcomere gene variants (SP+ and SP-), ALPK3tv carriers had a higher prevalence of apical/concentric patterns of hypertrophy (60%, P < 0.001) and of a short PR interval (10%, P = 0.009). Age at diagnosis and maximum left ventricular wall thickness were similar to SP- and left ventricular systolic impairment (6%) and non-sustained ventricular tachycardia (31%) at baseline similar to SP+. After 5.3 ± 5.7 years, 4 (9%) patients with ALPK3tv died of heart failure or had cardiac transplantation (log-rank P = 0.012 vs. SP- and P = 0.425 vs. SP+). Imaging and histopathology showed extensive myocardial fibrosis and myocyte vacuolation. CONCLUSIONS: Heterozygous ALPK3tv are pathogenic and segregate with a characteristic HCM phenotype.

Krapina atlases suggest a high prevalence of anatomical variations in the first cervical vertebra of Neanderthals.

The first cervical vertebra, atlas, and its anatomical variants have been widely studied in Homo sapiens. However, in Neanderthals, the presence of anatomical variants of the atlas has been very little studied until very recently. Only the Neanderthal group from the El Sidrón site (Spain) has been analysed with regard to the anatomical variants of the atlas. A high prevalence of anatomical variants has been described in this sample, which points to low genetic diversity in this Neanderthal group. Even so, the high prevalence of anatomical variations detected in El Sidrón Neanderthal atlases needs to be confirmed by analysing more Neanderthal remains. In this context, we analysed the possible presence of anatomical variants in the three Neanderthal atlases recovered from the Krapina site (Croatia) within the Neanderthal lineage. Two of the three Krapina atlases presented anatomical variations. One atlas (Krapina 98) had an unclosed transverse foramen and the other (Krapina 99) presented a non-fused anterior atlas arch. Moreover, an extended review of the bibliography also showed these anatomical variations in other Middle and Upper Pleistocene hominins, leading us to hypothesise that anatomical variations of the atlas had a higher prevalence in extinct hominins than in modern humans.

Three-dimensional geometric morphometrics of thorax-pelvis covariation and its potential for predicting the thorax morphology: A case study on Kebara 2 Neandertal.

The skeletal torso is a complex structure of outstanding importance in understanding human body shape evolution, but reconstruction usually entails an element of subjectivity as researchers apply their own anatomical expertise to the process. Among different fossil reconstruction methods, 3D geometric morphometric techniques have been increasingly used in the last decades. Two-block partial least squares analysis has shown great potential for predicting missing elements by exploiting the covariation between two structures (blocks) in a reference sample: one block can be predicted from the other one based on the strength of covariation between blocks. The first aim of this study is to test whether this predictive approach can be used for predicting thorax morphologies from pelvis morphologies within adult Homo sapiens reference samples with known covariation between the thorax and the pelvis. The second aim is to apply this method to Kebara 2 Neandertal (Israel, ∼60 ka) to predict its thorax morphology using two different pelvis reconstructions as predictors. We measured 134 true landmarks, 720 curve semilandmarks, and 160 surface semilandmarks on 60 3D virtual torso models segmented from CT scans. We conducted three two-block partial least squares analyses between the thorax (block 1) and the pelvis (block 2) based on the H. sapiens reference samples after performing generalized Procrustes superimposition on each block separately. Comparisons of these predictions in full shape space by means of Procrustes distances show that the male-only predictive model yields the most reliable predictions within modern humans. In addition, Kebara 2 thorax predictions based on this model concur with the thorax morphology proposed for Neandertals. The method presented here does not aim to replace other techniques, but to rather complement them through quantitative prediction of a virtual 'scaffold' to articulate the thoracic fossil elements, thus extending the potential of missing data estimation beyond the methods proposed in previous works.

Refinement Procedures for Clitorolabiaplasty in Male-to-Female Gender-Affirmation Surgery: More than an Aesthetic Procedure.

BACKGROUND: Among the various steps of a penile inversion feminizing genitoplasty, reconstruction of the clitoris and labia minora remains the most challenging procedure. AIM: This study aims to evaluate surgical outcomes of neoclitoroplasty performed before and after the introduction of the labia minora's creation in our surgical technique. METHODS: A retrospective analysis was carried out comparing 2 groups of patients that underwent penile inversion feminizing surgery: group A (64 patients) who had labia minora and clitoral hood creation and group B (103 patients) who did not. OUTCOMES: To describe the surgical technique and outcomes of clitorolabiaplasty in male-to-female gender-affirmation surgery. RESULTS: Concerning overall complication rates, there were significant differences in the incidence of hemorrhage and urethral stenosis (P < .01). Hemorrhage surrounding the urethra and labia was identified in 40 patients (group A: n = 8 [12.5%]; group B: n = 32 [31%]) (P = .006). Neomeatal stenosis occurred in 17 patients (group A: n = 1 [1.5%]; group B: n = 16 [15.5%]) (P = .003). Partial necrosis of the clitoris occurred in 2 cases (group A: n = 0; group B: n = 2 [1.9%]) (P = .52). Necrosis of the labia majora occurred in 3 cases (group A: n = 0; group B: n = 3 [2.9%]) (P = .28). 5 patients (group A: n = 2 (3.1%); group B: n = 3 [2.9%]) (P = .93) developed rectovaginal fistula. 6 patients experienced neovaginal canal stricture (group A: n = 3 [4.6%]; group B: n = 3 [2.9%]) (P = .54). 2 patients (group A: n = 0; group B: n = 2 [1.9%]) (P = .52) reported introital stenosis; Persistent granulation tissue inside the neovagina that required in-office treatments occurred in 4 cases (group A: n = 2 [3.1%]; group B: n = 2 [1.9%]) (P = .62). Wound dehiscence occurred in 23 patients (group A: n = 13 [20.3%]; group B: n = 10 [9.7%]) (P = .05). 24 patients (group A: n = 3 [4.6%]; group B: n = 21 [20.3%]) (P = .004) underwent 28 different types of aesthetic refinements. CLINICAL IMPLICATIONS: Incorporating the creation of labia minora and clitoral hood in one step is a safe and viable option in patients undergoing male-to-female gender-affirmation surgery. STRENGTHS & LIMITATIONS: Strength of the study is the large cohort of patients included and the consistent surgical technique. To our knowledge, this is the first study that compares with a control group, the introduction of labia minora creation in male-to-female gender-affirmation surgery. Limitations include the retrospective nature of the study and the absence of patient-reported outcomes measures. CONCLUSION: Technical refinements of our technique led to a significative reduction in urethral stenosis and postoperative hemorrhage without an increased risk of major complications. Raigosa M, Avvedimento S, Descarrega J, et al. Refinement Procedures for Clitorolabiaplasty in Male-to-Female Gender-Affirmation Surgery: More than an Aesthetic Procedure. J Sex Med 2020;17:2508-2517.

Assessing thoraco-pelvic covariation in Homo sapiens and Pan troglodytes: A 3D geometric morphometric approach.

OBJECTIVES: Understanding thoraco-pelvic integration in Homo sapiens and their closest living relatives (genus Pan) is of great importance within the context of human body shape evolution. However, studies assessing thoraco-pelvic covariation across Hominoidea species are scarce, although recent research would suggest shared covariation patterns in humans and chimpanzees but also species-specific features, with sexual dimorphism and allometry influencing thoraco-pelvic covariation in these taxa differently. MATERIAL AND METHODS: N = 30 adult H. sapiens and N = 10 adult Pan troglodytes torso 3D models were analyzed using 3D geometric morphometrics and linear measurements. Effects of sexual dimorphism and allometry on thoraco-pelvic covariation were assessed via regression analyses, and patterns of thoraco-pelvic covariation in humans and chimpanzees were computed via Two-Block Partial Least Squares analyses. RESULTS: Results confirm the existence of common aspects of thoraco-pelvic covariation in humans and chimpanzees, and also species-specific covariation in H. sapiens that is strongly influenced by sexual dimorphism and allometry. Species-specific covariation patterns in chimpanzees could not be confirmed because of the small sample size, but metrics point to a correspondence between the most caudal ribs and iliac crest morphology that would be irrespective of sex. CONCLUSIONS: This study suggests that humans and chimpanzees share common aspects of thoraco-pelvic covariation but might differ in others. In humans, torso integration is strongly influenced by sexual dimorphism and allometry, whilst in chimpanzees it may not be. This study also highlights the importance not only of torso widths but also of torso depths when describing patterns of thoraco-pelvic covariation in primates. Larger samples are necessary to support these interpretations.

3D geometric morphometric analysis of variation in the human lumbar spine.

OBJECTIVES: The shape of the human lumbar spine is considered to be a consequence of erect posture. In addition, several other factors such as sexual dimorphism and variation in genetic backgrounds also influence lumbar vertebral morphology. Here we use 3D geometric morphometrics (GM) to analyze the 3D morphology of the lumbar spine in different human populations, exploring those potential causes of variation. MATERIAL AND METHODS: We collected 390 (semi) landmarks from 3D models of the CT scans of lumbar spines of seven males and nine females from a Mediterranean population (Spain, Israel) and seven males and either females from a South African population for geometric morphometric (GM) analysis. We carried out Generalized Procrustes Analysis, Principal Components, and Regression analyses to evaluate shape variation; and complemented these analyses with the Cobb Method. RESULTS: The Mediterranean sample was considerably more lordotic than the South African sample. In both populations, female lumbar spines showed proportionally narrower and more craniocaudally elongated lumbar segments than in males. In addition, the point of maximum curvature in females tended to be located more inferiorly than in males. DISCUSSION: Our results show that sexual dimorphism is an important factor of lumbar spine variation that mainly affects features of lumbar spine robustness (height proportions) and the structure-but not the degree-of its curvature. Differences in lordosis, however, are clearer at the inter-population level. This reflects previous conflicting studies casting doubts on pregnancy as an adaptive factor influencing lordosis. Other factors, for example, shape of the individual lumbar vertebrae and intervertebral discs and their relative proportions within the lumbar spine should be considered when exploring variation in vertebral column morphology.

The Cardiomyopathy Registry of the EURObservational Research Programme of the European Society of Cardiology: baseline data and contemporary management of adult patients with cardiomyopathies.

Aims: The Cardiomyopathy Registry of the EURObservational Research Programme is a prospective, observational, and multinational registry of consecutive patients with four cardiomyopathy subtypes: hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and restrictive cardiomyopathy (RCM). We report the baseline characteristics and management of adults enrolled in the registry. Methods and results: A total of 3208 patients were enrolled by 69 centres in 18 countries [HCM (n = 1739); DCM (n = 1260); ARVC (n = 143); and RCM (n = 66)]. Differences between cardiomyopathy subtypes (P < 0.001) were observed for age at diagnosis, history of familial disease, history of sustained ventricular arrhythmia, use of magnetic resonance imaging or genetic testing, and implantation of defibrillators. When compared with probands, relatives had a lower age at diagnosis (P < 0.001), but a similar rate of symptoms and defibrillators. When compared with the Long-Term phase, patients of the Pilot phase (enrolled in more expert centres) had a more frequent rate of familial disease (P < 0.001), were more frequently diagnosed with a rare underlying disease (P < 0.001), and more frequently implanted with a defibrillator (P = 0.023). Comparing four geographical areas, patients from Southern Europe had a familial disease more frequently (P < 0.001), were more frequently diagnosed in the context of a family screening (P < 0.001), and more frequently diagnosed with a rare underlying disease (P < 0.001). Conclusion: By providing contemporary observational data on characteristics and management of patients with cardiomyopathies, the registry provides a platform for the evaluation of guideline implementation. Potential gaps with existing recommendations are discussed as well as some suggestions for improvement of health care provision in Europe.

Can the transverse foramen/vertebral artery ratio of double transverse foramen subjects be a risk for vertebrobasilar transient ischemic attacks?

The C6 is the cervical vertebra into which the vertebral artery enters the passage of the transverse foramen and it is the vertebra most affected by double transverse foramina. There is currently little information about the relation between the vertebral artery and the double transverse foramen in C6. We aimed to test whether subjects with a double transverse foramen in C6 have a reduced transverse foramen/vertebral artery ratio when compared with normal anatomy subjects who possess a single transverse foramen which may be a risk for transient vertebral artery stenosis. We measured the area of the transverse foramen and the vertebral artery in 27 double transverse and 56 normal anatomy subjects using computed tomography angiography. We found significant differences in the area of the transverse foramen between double transverse and normal subjects (P < 0.001) but not between the vertebral artery area of double transverse and normal subjects (P = 0.829). The subjects with double transverse foramina have a reduced transverse foramen/vertebral artery ratio, which may be a possible risk for transient vertebral artery stenosis.

The torso integration hypothesis revisited in Homo sapiens: Contributions to the understanding of hominin body shape evolution.

OBJECTIVES: Lower thoracic widths and curvatures track upper pelvic widths and iliac blades curvatures in hominins and other primates (torso integration hypothesis). However, recent studies suggest that sexual dimorphism could challenge this assumption in Homo sapiens. We test the torso integration hypothesis in two modern human populations, both considering and excluding the effect of sexual dimorphism. We further assess covariation patterns between different thoracic and pelvic levels, and we explore the allometric effects on torso shape variation. MATERIAL AND METHODS: A sex-balanced sample of 50 anatomically connected torsos (25 Mediterraneans, 25 Sub-Saharan Africans) was segmented from computed tomography scans. We compared the maximum medio-lateral width at seventh-ninth rib levels with pelvic bi-iliac breadth in males and females within both populations. We measured 1,030 (semi)landmarks on 3D torso models, and torso shape variation, mean size and shape comparisons, thoraco-pelvic covariation and allometric effects were quantified through 3D geometric morphometrics. RESULTS: Females show narrow thoraces and wide pelves and males show wide thoraces and narrow pelves, although this trend is more evident in Mediterraneans than in Sub-Saharans. Equal thoracic and pelvic widths, depths and curvatures were found in absence of sexual dimorphism. The highest strength of covariation was found between the lowest rib levels and the ilia, and allometric analyses showed that smaller torsos were wider than larger torsos. CONCLUSIONS: This is the first study testing statistically the torso integration hypothesis in anatomically connected torsos. We propose a new and more complex torso integration model in H. sapiens with sexual dimorphism leading to different thoracic and pelvic widths and curvatures. These findings have important implications in hominin body shape reconstructions.

Retrotransverse foramen of the atlas: prevalence and bony variations.

PURPOSE: To analyze the prevalence of the retrotransverse foramen (RTF) and its bony variations. METHODS: One hundred ten atlases of living adult subjects, 161 twentieth century dry adult cervical atlases and four dry adult cervical atlases from medieval skeletons were studied to detect the RTF and its abnormal bony variations. The 110 living adult subjects underwent a computed tomography study to detect the RTF. RESULTS: In the in vivo sample (n = 110; 100%), the RTF was found in four (3.6%) atlases. It was bilateral in all cases, but three (2.7%) patients showed complete RTF and the other patient presented a complete RTF in the left transverse process and an unclosed RTF in the right transverse process. In addition, the RTF was observed in combination with an unclosed transverse foramen in two cases (1.8%). In the twentieth century skeletal sample (n = 206; 100%) the RTF was found in 15 (7.3%) C1 vertebrae. It was bilateral in three (1.5%) vertebrae and unilateral in another 12 (5.8%) vertebrae. In the medieval skeletal sample (n = 4; 100%) one cadaveric atlas (25%) presented a bilateral RTF with special bony characteristics which presented an unexpected spicula in the left RTF. CONCLUSIONS: The RTF is a nonmetric variant of the atlas vertebra that can present non-degenerative and non-traumatic spiculae or it can be unclosed. In addition, it can be associated with the presence of unclosed transverse foramina.

D242N, a KV7.1 LQTS mutation uncovers a key residue for IKs voltage dependence.

KV7.1 and KCNE1 co-assemble to give rise to the IKs current, one of the most important repolarizing currents of the cardiac action potential. Its relevance is underscored by the identification of >500 mutations in KV7.1 and, at least, 36 in KCNE1, that cause Long QT Syndrome (LQTS). The aim of this study was to characterize the biophysical and cellular consequences of the D242N KV7.1 mutation associated with the LQTS. The mutation is located in the S4 transmembrane segment, within the voltage sensor of the KV7.1 channel, disrupting the conserved charge balance of this region. Perforated patch-clamp experiments show that, unexpectedly, the mutation did not disrupt the voltage-dependent activation but it removed the inactivation and slowed the activation kinetics of D242N KV7.1 channels. Biotinylation of cell-surface protein and co-immunoprecipitation experiments revealed that neither plasma membrane targeting nor co-assembly between KV7.1 and KCNE1 was altered by the mutation. However, the association of D242N KV7.1 with KCNE1 strongly shifted the voltage dependence of activation to more depolarized potentials (+50mV), hindering IKs current at physiologically relevant membrane potentials. Both functional and computational analysis suggest that the clinical phenotype of the LQTS patients carrying the D242N mutation is due to impaired action potential adaptation to exercise and, in particular, to increase in heart rate. Moreover, our data identify D242 aminoacidic position as a potential residue involved in the KCNE1-mediated regulation of the voltage dependence of activation of the KV7.1 channel.

COMPUTER ASSISTED RETINAL VESSEL TORTUOSITY EVALUATION IN NOVEL MUTATION FABRY DISEASE: Towards New Prognostic Markers.

PURPOSE: Fabry disease is a rare lysosomal storage disorder with systemic involvement. The authors report on a large Fabry family with GLA p.M187R mutation and exhaustive ophthalmologic assessment. METHODS: Comprehensive systemic evaluation and genetic diagnosis were performed. Ophthalmologic evaluation included intraocular pressure/visual acuity measurement, refractometry, slit lamp examination, retinography, and optical coherence tomography. Three parameters quantified retinal vessel tortuosity: sum of angle metrics, product of angle distance, and triangular index. Calculations were semiautomatized using dedicated software. RESULTS: Ten individuals (2 males and 8 females) were described. Seventy-five percent had retinal vessel tortuosity. One hundred percent had cornea verticillata. Perimacular vessels were predominantly involved. The correlation between the right and left eye tortuosity measurements was very tight. A significant correlation between retinal vessel tortuosity and systemic severity measured by general Mainz Severity Score Index (MSSI), renal MSSI, and neurological MSSI but no cardiac MSSI was observed. Right sum of angle metrics value was an independent statistical predictor of the general-MSSI score in presence of age. CONCLUSION: p.M187R mutation causes a severe systemic and ophthalmologic phenotype, in both male and female patients. Semiautomatic assessment of retinal vessel tortuosity is an objective and reproducible tool. All three parameters of tortuosity are closely associated with Fabry severity scores. Studies of larger series are being awaited to establish the role of retinal vessel tortuosity as a noninvasive marker of disease progression.

Acute headache attributed to whiplash in arcuate foramen and non-arcuate foramen subjects.

PURPOSE: To test the association between arcuate foramen (AF) in the first cervical vertebra with acute headache attributed to whiplash. METHODS: Retrospective study of 128 patients that suffered a whiplash. The presence or absence of AF was recorded after a radiographic study, as well as the presence or absence of acute headache after the whiplash. RESULTS: The frequency of AF was 17.2%. Patients with bilateral AF presented a significant (p = 0.000, Fisher's test) increase in the frequency of acute headache (90.9%) in comparison with the non-AF group (5.7%). The ratio between the presence and absence of acute headache was 166.6 times higher (IC 95% 18.2-1526.22) in subjects with bilateral AF in comparison with non-AF subjects. CONCLUSIONS: The presence of bilateral AF is associated to an increased frequency of acute headache after suffering a whiplash, information of interest for the attention to these patients.

Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC working group on myocardial and pericardial diseases.

In this paper the Working Group on Myocardial and Pericardial Disease proposes a revised definition of dilated cardiomyopathy (DCM) in an attempt to bridge the gap between our recent understanding of the disease spectrum and its clinical presentation in relatives, which is key for early diagnosis and the institution of potential preventative measures. We also provide practical hints to identify subsets of the DCM syndrome where aetiology directed management has great clinical relevance.