Revascularisation of Chronic Limb Threatening Ischaemia in Patients with no Pedal Arteries Leads to Lower Midterm Limb Salvage

Objective: Chronic limb threatening ischaemia (CLTI) involving the infragenicular arteries is treated by distal angioplasty or pedal bypass; however, this is not always possible, due to chronically occluded pedal arteries (no patent pedal artery, N-PPA). This pattern represents a hurdle to successful revascularisation, which must be limited to the proximal arteries. The aim of the study was to analyse the outcome of patients with CLTI and N-PPA after a proximal revascularisation.Methods: All patients with CLTI submitted to revascularisation in a single centre (2019 - 2020) were analysed. All angiograms were reviewed to identify N-PPA, defined as total obstruction of all pedal arteries. Revascularisation was performed with proximal surgical, endovascular, and hybrid procedures. Early and midterm survival, wound healing, limb salvage, and patency rates were compared between N-PPA and patients with one or more patent pedal artery (PPA).Results: Two hundred and eighteen procedures were performed. One hundred and forty of 218 (64.2%) patients were male, mean age 73.2 & PLUSMN; 10.6 years. The procedure was surgical in 64/218 (29.4%) cases, endovascular in 138/218 (63.3%), and hybrid in 16/218 (7.3%). N-PPA was present in 60/218 (27.5%) cases. Eleven of 60 (18.3%) cases were treated surgically, 43/60 (71.7%) by endovascular and 6/60 (10%) by hybrid procedures. Technical success was similar in the two groups (N-PPA 85% vs. PPA 82.3%, p = .42). At a mean follow up of 24.5 & PLUSMN; 10.2 months, survival (N-PPA 93.7 & PLUSMN; 3.5% vs. PPA 95.3 & PLUSMN; 2.1%, p = .22) and primary patency (N-PPA 53.1 & PLUSMN; 8.1% vs. PPA 55.2 & PLUSMN; 5%, p = .56) were similar. Limb salvage was significantly lower in N-PPA patients (N-PPA 71.4 & PLUSMN; 6.6% vs. PPA 81.5 & PLUSMN; 3.4%, p = .042); N-PPA was an independent predictor of major amputation (hazard ratio [HR] 2.02, 1.07 - 3.82, p = .038) together with age > 73 years (HR 2.32, 1.17 4.57, p = .012) and haemodialysis (2.84, 1.48 - 5.43, p = .002).Conclusion: N-PPA is not uncommon in patients with CLTI. This condition does not hamper technical success, primary patency, and midterm survival; however, midterm limb salvage is significantly lower than in patients with PPA. This should be considered in the decision making process

Local inference for functional data on manifold domains using permutation tests

Pini and Vantini (2017) introduced the interval-wise testing procedure which performs local inference for functional data defined on an interval domain, where the output is an adjusted p-value function that controls for type I errors. We extend this idea to a general setting where domain is a Riemannian manifolds. This requires new methodology such as how to define adjustment sets on product manifolds and how to approximate the test statistic when the domain has non-zero curvature. We propose to use permutation tests for inference and apply the procedure in three settings: a simulation on a "chameleon-shaped" manifold and two applications related to climate change where the manifolds are a complex subset of $S^2$ and $S^2 \times S^1$, respectively. We note the tradeoff between type I and type II errors: increasing the adjustment set reduces the type I error but also results in smaller areas of significance. However, some areas still remain significant even at maximal adjustment

Gaussian graphical modeling for spectrometric data analysis

Motivated by the analysis of spectrometric data, we introduce a Gaussian graphical model for learning the dependence structure among frequency bands of the infrared absorbance spectrum. The spectra are modeled as continuous functional data through a B-spline basis expansion and a Gaussian graphical model is assumed as a prior specification for the smoothing coefficients to induce sparsity in their precision matrix. Bayesian inference is carried out to simultaneously smooth the curves and to estimate the conditional independence structure between portions of the functional domain. The proposed model is applied to the analysis of infrared absorbance spectra of strawberry purees

A Geometrical-Statistical Approach to Outlier Removal for TDOA Measurements

The curse of outlier measurements in estimation problems is a well-known issue in a variety of fields. Therefore, outlier removal procedures, which enables the identification of spurious measurements within a set, have been developed for many different scenarios and applications. In this paper, we propose a statistically motivated outlier removal algorithm for time differences of arrival (TDOAs), or equivalently range differences (RD), acquired at sensor arrays. The method exploits the TDOA-space formalism and works by only knowing relative sensor positions. As the proposed method is completely independent from the application for which measurements are used, it can be reliably used to identify outliers within a set of TDOA/RD measurements in different fields (e.g., acoustic source localization, sensor synchronization, radar, remote sensing, etc.). The proposed outlier removal algorithm is validated by means of synthetic simulations and real experiments

Exploring resting-state functional connectivity invariants across the lifespan in healthy people by means of a recently proposed graph theoretical model

In this paper we investigate the changes in the functional connectivity intensity, and some related properties, in healthy people, across the life span and at resting state. For the explicit computation of the functional connectivity we exploit a recently proposed model, that bases not only on the correlations data provided by the acquisition equipment, but also on different parameters, such as the anatomical distances between nodes and their degrees. The leading purpose of the paper is to show that the proposed approach is able to recover the main aspects of resting state condition known from the available literature, as well as to suggest new insights, perspectives and speculations from a neurobiological point of view. Our study involves 133 subjects, both males and females of different ages, with no evidence of neurological diseases or systemic disorders. First, we show how the model applies to the sample, where the subjects are grouped into 28 different groups (14 of males and 14 of females), according to their age. This leads to the construction of two graphs (one for males and one for females), that can be realistically interpreted as representative of the neural network during the resting state. Second, following the idea that the brain network is better understood by focusing on specific nodes having a kind of centrality, we refine the two output graphs by introducing a new metric that favours the selection of nodes having higher degrees. As a third step, we extensively comment and discuss the obtained results. In particular, it is remarkable that, despite a great overlapping exists between the outcomes concerning males and females, some intriguing differences appear. This motivates a deeper local investigation, which represents the fourth part of the paper, carried out through a thorough statistical analysis. As a result, we are enabled to support that, for two special age groups, a few links contribute in differentiating the behaviour of males and females. In addition, we performed an average-based comparison between the proposed model and the traditional statistical correlation-based approach, then discussing and commenting the main outlined discrepancies

Relaxin prevents cardiac fibroblast-myofibroblast transition via Notch-1-mediated Inhibition of TGF-β/Smad3 signaling

The hormone relaxin (RLX) is produced by the heart and has beneficial actions on the cardiovascular system. We previously demonstrated that RLX stimulates mouse neonatal cardiomyocyte growth, suggesting its involvement in endogenous mechanisms of myocardial histogenesis and regeneration. In the present study, we extended the experimentation by evaluating the effects of RLX on primary cultures of neonatal cardiac stromal cells. RLX inhibited TGF-β1-induced fibroblast-myofibroblast transition, as judged by its ability to down-regulate α-smooth muscle actin and type I collagen expression. We also found that the hormone up-regulated metalloprotease (MMP)-2 and MMP-9 expression and downregulated the tissue inhibitor of metalloproteinases (TIMP)-2 in TGF-β1-stimulated cells. Interestingly, the effects of RLX on cardiac fibroblasts involved the activation of Notch-1 pathway. Indeed, Notch-1 expression was significantly decreased in TGF-β1-stimulatedfibroblasts as compared to the unstimulated controls; this reduction was prevented by the addition of RLX to TGF-β1-stimulated cells. Moreover, pharmacological inhibition of endogenous Notch-1 signaling by N-3,5-difluorophenyl acetyl-L-alanyl-2-phenylglycine-1,1-dimethylethyl ester (DAPT), a γ-secretase specific inhibitor, as well as the silencing of Notch-1 ligand, Jagged-1, potentiated TGF-β1-induced myofibroblast differentiation and abrogated the inhibitory effects of RLX. Interestingly, RLX and Notch-1 exerted their inhibitory effects by interfering with TGF-β1 signaling, since the addition of RLX to TGF-β1-stimulated cells caused a significant decrease in Smad3 phosphorylation, a typical downstream event of TGF-β1 receptor activation, while the treatment with a prevented this effect. These data suggest that Notch signaling can down-regulate TGF-β1/Smad3-induced fibroblast-myofibroblast transition and that RLX could exert its well known anti-fibrotic action through the up-regulation of this pathway. In conclusion, the results of the present study beside supporting the role of RLX in the field of cardiac fibrosis, provide novel experimental evidence on the molecular mechanisms underlying its effects

Trabecular bone score and bone turnover markers in men with DISH: Data from the Camargo Cohort study

Objective: Diffuse idiopathic skeletal hyperostosis (DISH) has been associated with an increased risk of vertebral fracture. To date, no studies have investigated the relationship between DISH and bone microstructure assessed by the trabecular bone score (TBS). Methods: Cross-sectional study, nested in a prospective population-based cohort. All men (968) aged?50 years were included. Clinical covariates, DISH, TBS, serum bone turnover markers and bone mineral density (BMD) were analyzed. Results: Mean age of participants was 65 ± 9 years. 207 (21.6%) had DISH. DISH subjects were older, had higher body mass index (BMI) and abdominal perimeter, lower glomerular filtration rate (GFR), and higher prevalence of metabolic syndrome (MetS) than non-DISH (NDISH) subjects. Bone mineral density at the lumbar spine (LS-BMD) was significantly higher in the DISH group. TBS values were 1.317 [1.303-1.331] for DISH and 1.334 [1.327-1.341] for NDISH subjects, after adjusting by age, BMI, abdominal perimeter, arterial hypertension, diabetes mellitus, MetS, GFR, serum alkaline phosphatase (ALP), LS and femoral neck BMD (p = 0.03). Serum ALP levels were higher in DISH subjects, showing an inverse correlation with TBS that remained significant after adjusting by age and BMI. Conclusions: TBS values were significantly lower in men with DISH irrespective of age, BMI and BMD, suggesting that the presence of DISH might be related to a worse trabecular microstructureThe study has been funded by grants from the Instituto de Salud Carlos III (PI18/00762), Ministerio de Ciencia, Innovacion y Universidades, Spain, that included FEDER funds from the EU

Development and validation of the ID-EC - The ITALIAN version of the identify chronic migraine

Background: Case-finding tools, such as the Identify Chronic Migraine (ID-CM) questionnaire, can improve detection of CM and alleviate its significant societal burden. We aimed to develop and validate the Italian version of the ID-CM (ID-EC) in paper and as a smart app version in a headache clinic-based setting. Methods: The study investigators translated and adapted to the Italian language the original ID-CM questionnaire (ID-EC) and further implemented it as a smart app. The ID-EC was tested in its paper and electronic version in consecutive patients referring to 9 Italian tertiary headache centers for their first in-person visit. The scoring algorithm of the ID-EC paper version was applied by the study investigators (case-finding) and by patients (self-diagnosis), while the smart app provided to patients automatically the diagnosis. Diagnostic accuracy of the ID-EC was assessed by matching the questionnaire results with the interview-based diagnoses performed by the headache specialists during the visit according to the criteria of International Classification of Headache Disorders, III edition, beta version. Results: We enrolled 531 patients in the test of the paper version of ID-EC and 427 in the validation study of the smart app. According to the clinical diagnosis 209 patients had CM in the paper version study and 202 had CM in the smart app study. 79.5% of patients returned valid paper questionnaires, while 100% of patients returned valid and complete smart app questionnaires. The paper questionnaire had a 81.5% sensitivity and a 81.1% specificity for case-finding and a 30.7% sensitivity and 90.7% specificity for self-diagnosis, while the smart app had a 64.9% sensitivity and 90.2% specificity. Conclusions: Our data suggest that the ID-EC, developed and validated in tertiary headache centers, is a valid case-finding tool for CM, with sensitivity and specificity values above 80% in paper form, while the ID-EC smart app is more useful to exclude CM diagnosis in case of a negative result. Further studies are warranted to assess the diagnostic accuracy of the ID-EC in general practice and population-based settings