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Objective: To appraise the highest evidence on hip morphology as a risk factor for developing hip osteoarthritis (OA).Design: We searched for studies evaluating the association between radiological hip morphology parameters and the prevalence, incidence or progression of hip OA (based on different radiographic and clinical criteria) in the MEDLINE, EMBASE, Web of Science, Scopus, Cochrane Library and PEDro databases from inception until June 2020. Prospective and cross-sectional studies were separately evaluated. Data are presented as odds ratios (OR) with 95% confidence intervals (CI).Results: We included 9 prospective and 21 cross-sectional studies in the meta-analysis, and evaluated 42,831 hips from 25,898 individuals (mean age: 59 years). Prospective studies showed that, compared with control hips, hips with cam morphology (alpha angle >60°; OR = 2.52, 95% CI: 1.83 to 3.46, P < 0.001) or hip dysplasia (lateral center-edge angle (LCEA) <25°; OR = 2.38, 95% CI: 1.84 to 3.07, P < 0.001), but not hips with pincer morphology (LCEA >39°; OR = 1.08, 95% CI: 0.57 to 2.07, P = 0.810), were more likely to develop hip OA than hips without these morphologies. Cross-sectional studies showed a greater prevalence of pincer morphology (LCEA >39°, OR = 3.71, 95% CI: 2.98 to 4.61, P < 0.001) and acetabular retroversion (crossover sign; OR = 2.65, 95% CI: 1.17 to 6.03, P = 0.020) in hips with OA than in control hips.Conclusion: Cam morphology and hip dysplasia were consistently associated with the development of hip OA. Pincer morphology was associated with hip OA in cross-sectional but not in prospective studies. The heterogeneous quantification of pincer morphology on radiographs limits a clear conclusion on its association with hip OA. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA) is a deadly cancer with limited treatment options. The development of new therapies is urgently needed and Organ-On-Chip has emerged as a promising tool for studying diseases in a more reliable 3D environment. In this study, we evaluated the reliability of CCA-on-chip as a patient-specific platform by integrating the immune cells and assessing their migration based on patient characteristics. Primary CCA cells were isolated from surgically resected patients at Humanitas Research Hospital. The CCA microenvironment was recapitulated in the device by co-culturing CCA cells and cancer-associated fibroblasts (CAFs) in the central channel, flanked by endothelial cells in one lateral channel. T-cells exhibited a high ability to migrate within the tumor niche, spreading throughout the central channel. Two culture conditions were compared to investigate the influence of crosstalk between CCA cells and CAFs on T-cell migration. In the monoculture, T-cells showed greater trafficking compared to the co-culture. Furthermore, T-cells formed aggregates surrounding tumor spheroids in the monoculture, while they appeared dispersed in the co-culture. Interestingly, the co-culture exhibited higher levels of immunosuppressive molecules, suggesting that CAFs could contribute to an immunosuppressive microenvironment. Furthermore, in immunohistochemistry, CCA patient-derived cells were divided into two groups according to CD3+ cells: high-infiltrating (HOT) patients showed increased T-cell migration compared to low-infiltrating (COLD) patients. T-cells exhibited higher migration in the monoculture in HOT and COLD patients compared to their respective co-culture, further corroborating the role of CAFs in influencing immune cell recruitment and immunosuppression. Indeed, the expression of chemoattractant or immunosuppressive molecules, such as CXCL9, CXCL10, IL6 and IL10, varied between HOT and COLD patients and between culture conditions, suggesting their roles in immune cell recruitment and immunosuppression. Our CCA-on-chip platform recapitulates the heterogeneity of the tumor microenvironment, demonstrating differences in T-cell trafficking and the expression of immunomodulatory molecules between high-infiltrating and low-infiltrating patients. [ABSTRACT FROM AUTHOR]

Background: Increased postural balance challenge is associated with more fluctuations in centre of pressure movement, indicating increased interference from the postural control system. The role of intrinsic foot muscles in balance control is relatively understudied and whether such control system interference occurs at the level of these muscles is unknown.Research Question: Do fewer fluctuations in intrinsic foot muscle excitation occur in response to increased postural balance challenge?Methods: Surface EMGs were recorded using a grid of 13 × 5 channels from the plantar surface of the foot of 17 participants, who completed three balance tasks: bipedal stance; single leg stance and bipedal tip-toe. Centre of pressure (CoP) movement was calculated from simultaneously recorded force plate signals. Fluctuations in CoP and EMGs for each task were quantified using a sample entropy based metric, Entropy Halflife (EnHL). Longer EnHL indicates fewer signal fluctuations.Results: The shortest EMG EnHL, 9.27 ± 3.34 ms (median ± interquartile range), occurred during bipedal stance and the longest during bipedal tip-toe 15.46 ± 11.16 ms, with 18.80 ± 8.00 ms recorded for single leg stance. Differences were statistically significant between bipedal stance and both bipedal tip-toe (p < 0.001) and single leg stance (p < 0.001). CoP EnHL for both anterior-posterior and medial-lateral movements also differed significantly between tasks (p < 0.001, both cases). However, anterior-posterior CoP EnHL was longest for bipedal stance 259.84±230.22 ms and shortest for bipedal tip-toe 146.25±73.35 ms. Medial-lateral CoP EnHL was also longest during bipedal stance 215.73±187.58 ms, but shortest for single leg stance 113.48±83.01 ms.Significance: Fewer fluctuations in intrinsic foot muscle excitation occur in response to increased postural balance challenge. Fluctuations in CoP movement during balance must be predominantly driven by excitation of muscles extrinsic to the foot. Intrinsic foot muscles therefore likely play a greater role in stabilisation of the foot than balance control during the postural tasks studied. [ABSTRACT FROM AUTHOR]

• Radio Guided Surgery can be performed in the abdomen with beta- emission. • In such complex environment electrons outperform gammas. • Electrons locality allows to define an effective threshold for tumor discrimination. • Ex-vivo tests on tumor samples are used to define and test the threshold. This paper provides a first insight of the potential of the β - Radio Guided Surgery ( β - -RGS) in a complex surgical environment like the abdomen, where multiple sources of background concur to the signal at the tumor site. This case is well reproduced by ex-vivo samples of 90 Y -marked Gastro-Entero-Pancreatic Neuroendocrine Tumors (GEP NET) in the bowel. These specimens indeed include at least three wide independent sources of background associated to three anatomical districts (mesentery, intestine, mucose). The study is based on the analysis of 37 lesions found on 5 samples belonging to 5 different patients. We show that the use of electrons, a short range particle, instead of γ particles, allows to limit counts read on a lesion to the sum of the tumor signal plus the background generated by the sole hosting district. The background on adjacent districts in the same specimen/patient is found to differ up to a factor 4, showing how the specificity and sensitivity of the β - -RGS technique can be fully exploited only upon a correct measurement of the contributing background. This locality has been used to set a site-specific cut-off algorithm to discriminate tumor and healthy tissue with a specificity of 100% and a sensitivity, on this test data sample, close to 100%. Factors influencing the sensitivity are also discussed. One of the specimens set allowed us evaluate the volume of the lesions, thus concluding that the probe was able to detect lesions as small as 0.04 mL in that particular case. [ABSTRACT FROM AUTHOR]

• Different segmentation pipelines may provide inconsistent quantification of brain structures. • The intra- and inter-method agreement between two popular segmentation software packages SPM12 and FreeSurfer v6.0. • SPM provides more consistent results both in the intra- and the inter-method agreement evaluation. • There are consistent biases in the estimates of gray matter and white matter between SPM and FreeSurfer. • To cross-validate the findings of each study against different segmentation methods before interpreting of the results. The lack of inter-method agreement can produce inconsistent results in neuroimaging studies. We evaluated the intra-method repeatability and the inter-method reproducibility of two widely-used automatic segmentation methods for brain MRI: the FreeSurfer (FS) and the Statistical Parametric Mapping (SPM) software packages. We segmented the gray matter (GM), the white matter (WM) and subcortical structures in test-retest MRI data of healthy volunteers from Kirby-21 and OASIS datasets. We used Pearson's correlation (r), Bland-Altman plot and Dice index to study intra-method repeatability and inter-method reproducibility. In order to test whether different processing methods affect the results of a neuroimaging-based group study, we carried out a statistical comparison between male and female volume measures. A high correlation was found between test-retest volume measures for both SPM (r in the 0.98–0.99 range) and FS (r in the 0.95–0.99 range). A non-null bias between test-retest FS volumes was detected for GM and WM in the OASIS dataset. The inter-method reproducibility analysis measured volume correlation values in the 0.72–0.98 range and the overlap between the segmented structures assessed by the Dice index was in the 0.76–0.83 range. SPM systematically provided significantly greater GM volumes and lower WM and subcortical volumes with respect to FS. In the male vs. female brain volume comparisons, inconsistencies arose for the OASIS dataset, where the gender-related differences appear subtler with respect to the Kirby dataset. The inter-method reproducibility should be evaluated before interpreting the results of neuroimaging studies. [ABSTRACT FROM AUTHOR]

Atrial septal defect (ASD) is the most common adult congenital heart disease. The left-to-right shunt causes a right ventricular (RV) volume overload. Only little is known about RV remodeling after ASD closure. We aimed to assess RV function using 2D, 3D echocardiography and 3D RV strain before and 1 month after ASD closure. We prospectively included in this monocentric study 9 patients with secundum ASD who underwent percutaneous closure between September 2019 and January 2020. 2D and 3D Echocardiography were performed in all patients before and 1-month after closure. While we initially planned to collect echocardiographic data 3- and 6-months after ASD closure, the COVID-19 pandemic made this impossible. All patients gave their informed consent to the study. Clinical and ultrasound data were collected and anonymized. 3D RV echocardiographic sequences were analyzed by semi-automatic software (Tomtec 4D RV Function, Unterschleissheim, Germany) and output meshes were post-processed to extract regional deformation. Patients' mean age was 31.0 ± 12.3 years, 44.4% were female. Mean ASD diameter was 16.6 ± 7.4 mm. RV end diastolic diameter and right atrial (RA) area were significantly larger than normal values and decreased significantly after ASD closure (45.8 ± 4.9 vs. 37.8 ± 5.7 mm; P = 0.0009 and 21.4 ± 4.2 vs. 16.3 ± 2.7 cm2; P = 0.01, respectively). 3D RV volumes were significantly lower after ASD closure; respectively 156.3 ± 61.7 vs. 82.9 ± 17.40 mL, P = 0.02 for end diastolic volume and 59.4 ± 19.3 vs. 32.6 ± 9.2 mL, P = 0.01 for end systolic volume. RV function decreases after ASD closure as illustrated by TAPSE (23.3 ± 6.0 vs. 29.1 ± 4.2 mm, P = 0.03) as well as 3D RV strain with a significantly decreased in area strain, longitudinal strain as well as circumferential strain (respectively P = 0.006, P = 0.009 and P = 0.02) (Fig. 1). After percutaneous ASD closure, we demonstrate a decrease in RV function in all strain components using 3D strain. This decrease in RV strain probably illustrates the decrease in RV parietal stretch related to the normalization of RV loading conditions. 3D strain can be useful to assess the RV function evolution in response to different loading conditions. [ABSTRACT FROM AUTHOR]

Acute heart failure is the most frequent reason for hospitalization in people over 65-years-old. The burden on public health justifies the development of tools relevant to diagnose and optimize its treatment. Left atrial reservoir peak strain (PALS) has shown an excellent correlation with left ventricular filling pressures (LVFP) measured invasively but its evolution during hospitalization for heart failure has never been studied. The aim of our study is to investigate the evolution of PALS in patients hospitalized for acute heart failure and its correlation with the usual clinical and biological ultrasound parameters. We included in this study 19 patients hospitalized for acute heart failure in the cardiology department of the Nice University Hospital. Clinical, biological and echocardiographic data were collected daily during the hospitalization. PALS was measured using the 4 chambers view (Tomtec 2D STRAIN, Unterschleissheim, Germany). Our results show that PALS is feasible and reproducible. The average PALS over the first two days was low, below 15% (threshold previously established as best correlated with increased LVFP) and exceeded this threshold by the third day of treatment. No correlation was found between PALS and other ultrasound parameters on admission or during the hospital course. PALS is the only ultrasound marker whose evolution is correlated to the evolution of BNP. The threshold of 12.5%, determined by a ROC curve, was the most discriminating for the prediction of clinically increased LVFP (AUC: 0.680). Using this threshold in the 68% of patients in the grey area of the E/E' ratio and the 41% of patients with low or indeterminate LVFP according to the current algorithm, we reduce the inaccuracy rate by respectively 5 and 20%. The results obtained in the determination of PALS on admission and during hospitalization are consistent with previous studies. In our study, PALS is an independent marker of clinically increased LVFP. PALS allowed to increase the sensitivity of echo to detect increased LVFP and remain useful throughout the acute heart failure hospitalization as it is correlated with BNP and could help monitoring the therapy efficacy. [ABSTRACT FROM AUTHOR]

Intrinsic foot muscles (IFM) are a crucial component within the human foot. Investigating their functioning can help understand healthy and pathological behaviour of foot and ankle, fundamental for everyday activities. Recording muscle activation from IFM has been attempted with invasive techniques, mainly investigating single muscles. Here we present a novel methodology, to investigate the feasibility of recording physiological surface EMG (sEMG) non-invasively and quantify patterns of activation across the whole plantar region of the foot. sEMG were recorded with a 13 × 5 array from the sole of the foot (n = 25) during two-foot stance, two-foot tiptoe and anterior/posterior sways. Physiological features of sEMG were analysed. During anterior/posterior epochs within the sway task, sEMG patterns were analysed in terms of signal amplitude (intensity) and structure (Sample Entropy) distribution, by evaluating the centre of gravity (CoG) of each topographical map. Results suggest signals are physiological and not affected by loading. Both amplitude and sample entropy CoG coordinates were grouped in one region and overlapped, suggesting that the region with highest amplitude corresponds with the most predictable signal. Therefore, both spatial and temporal features of IFM activation may be recorded non-invasively, providing opportunity for more detailed investigation of IFM function in healthy and patient populations. [ABSTRACT FROM AUTHOR]

Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer of biliary epithelium with generally unsuccessful therapeutic options. This highlights the importance of deeper decipher iCCA mechanisms to develop new effective therapeutic strategies. Nevertheless, in-vivo cell interaction complexity has hindered an effective recapitulation of the in-vitro human milieu through 2D culture systems. In the last years, strong efforts were focused on the Organ-On-Chip (OoC) as promising models to faithfully recapitulate the in-vivo tumor niche. In this study, we aimed to develop an in-vitro 3D microfluidic device by co-culturing three cell types involved in iCCA. Primary iCCA cells were isolated from patients surgically resected at Humanitas Research Hospital. The microfluidic device was fabricated at Polytechnic of Milan, composed of three microfluidically interconnected channels. iCCA microenvironment was recapitulated by co-culturing iCCA cells and cancer-associated fibroblasts (CAFs) in the central channel with an ad hoc medium and embedded in an optimized hydrogel, flanked by an endothelial tubule in the lateral channel. The 3D cellular organization was visualized using confocal microscopy and the significant increase in the expression of key phenotypic cell markers was assessed by q RT-PCR, compared to 2D culture system. Diffusion assays at small and large molecules showed the high biocompatibility of this platform and the functional integrity of the endothelial tubule. Subsequently, the mechanical and biological proprieties of the platform were evaluated overtime in culture, showing that the cross-talk established between iCCA cells and CAFs within the chip led to a deep extracellular matrix remodeling. Indeed, scanning electron microscopy (SEM) allowed to measure the dimension of the matrix pores and immunofluorescence assay revealed a significant increase in the collagen IV deposition within the hydrogel. Our results showed that iCCA-on-chip provides a reliable 3D platform able to mimic the in-vivo iCCA microenvironment and may represent useful tool to investigate patient-specific therapeutic strategies. [ABSTRACT FROM AUTHOR]

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Abstract: In the Italian oenological industry, the regular practice used to naturally increase the colour of red wines consists in blending them with a wine very rich in anthocyanins, namely Rossissimo. In the Asian market, on the other hand, anthocyanins extracted by black rice are frequently used as correctors for wine colour. This practice does not produce negative effects on health; however, in many countries, it is considered as a food adulteration. The present study is therefore aimed to discriminate wines containing anthocyanins originated from black rice and grapevine by using reliable spectroscopic techniques requiring minimum sample preparation. Two series of samples have been prepared from five original wines, that were added with different amounts of Rossissimo or of black rice anthocyanins solution, until the desired Colour Index was reached. The samples have been analysed by FT-NIR and 1H NMR spectroscopies and the resulting spectra matrices were subjected to multivariate classification. Initially, PLS-DA was used as classification method, then also variable selection/classification methods were applied, i.e. iPLS-DA and WILMA-D. The classification with variable selection of NIR spectra permitted to classify the test set samples with an efficiency of about 70%. Probably these not excellent performances are due to the matrix effect, together with the lack of sensitivity of NIR with respect to minor compounds. On the contrary, very satisfactory results were obtained on NMR spectra in the aromatic region between 6.5 and 9.5ppm. The classification method based on wavelet-based variables selection, permitted to reach an efficiency in validation greater than 95%. Finally, 2D correlation analysis was applied to FT-NIR and 1H NMR matrices, in order to recognise the spectral zones bringing the same chemical information. [Copyright &y& Elsevier]

Abstract: Since 1990 FN S.p.A (a 98.65% ENEA participated Company), in collaboration with ENEA and AFCo-Ansaldo Fuel Cells Company, has been involved in research and development activities in the field of high temperature fuel cell porous components and in their traditional manufacturing processes (tape casting and sintering). In alternative to the traditional tape casting technology, FN has developed an innovative process based on the moulding plastic technology for the production of MCFC ceramic matrixes. With the new technology the environmental impact is reduced as it has been shown by LCA (Life Cycle Assessment) preliminary studies. These results are not the only advantages: the new process allows the realization of various and/or complex component shapes, a higher productivity level, cost reducing and the complete re-workability of rejects. In this paper a comparison between the traditional tape casting process and the new route process is shown. [Copyright &y& Elsevier]

Abstract: In order to evaluate the effects of some neuro-endocrine changes during aging we have studied adrenal, thyroid and pineal secretion in young, healthy old and centenarians. The number of subjects in each hormone group varied. The following parameters were evaluated: serum levels of cortisol, dehydroepiandrosterone-sulfate (DHEAS), free triiodothyronine (FT3), thyroxine (FT4), reverse triiodothyronine (rT3) and thyroid-stimulating hormone (TSH). Urinary 6-hydroxymelatonin sulfate (aMT6s) and free cortisol were measured twice daily. Centenarians exhibited significantly lower TSH levels together with slightly higher rT3 levels than old controls. These changes could be due to reduced 5′-deiodinase activity occurring also in absence of substantial changes of the nutritional pattern. Morning serum cortisol levels were found to be similar in the 3 age groups, whereas the decline of serum DHEAS levels was well evident also after the ninth decade of life. The cortisol/DHEAS molar ratio, which usually increases with age and considered to be an expression of a neurotoxic pattern of the steroidal milieu in the central nervous system, did not shown any further increase in centenarians. The urinary free cortisol and aMT6s excretion declined with age; however only in centenarians and in young controls aMT6s excretion was significantly higher at night than during the day. These findings suggest that the circadian rhythm of melatonin secretion is maintained in centenarians and, based on the limitations of this study, could be considered one factor in successful aging. [Copyright &y& Elsevier]

Survival in pulmonary arterial hypertension (PAH) relates to right ventricular (RV) function. Whereas prognosis differs widely between PAH associated with congenital heart disease (CHD) and other causes of PAH, only little is known about differences in RV function. We aimed at comparing RV function assessed by 3D-speckle-tracking in patients with CHD-PAH, other PAH aetiologies and healthy controls; and assess the relationship between ventricular function and prognostic parameters. We performed a prospective multi-centric study between June 2015 and June 2017 recruiting 27 patients with CHD-PAH (3 had closed shunts, 24 had Eisenmenger syndrome; among these, 11 had a pre-tricuspid shunt, 13 had a post-tricuspid shunt), to compare with 27 group 1 non-CHD related-PAH patients (nPAH) and 27 controls matched on age and sex with the CHD-PAH group. Patients with complex CHD were excluded. All patients underwent 2D and 3D transthoracic echocardiography at baseline. 3D RV echocardiographic sequences were analysed by a commercial RV-specific software and output meshes were post-processed to extract deformation data. There was no significant age difference between the subgroups. In CHD-PAH patients, RV global area and longitudinal strain did not significantly differ as compared to nPAH but RV global circumferential strain was significantly better (P = 0.006). All strain components were impaired as compared to controls (P < 0.0001). In the whole patient population, over a mean follow-up of 27.6 ± 13.3 months, 10 patients (17.5%) died from PAH or were transplanted (including 2 patients with CHD-PAH). Global RV circumferential strain was significantly associated to death or transplant (P = 0.004, AUC 0.823; HR 1.41[1.09–1.81]) (Fig. 1). RV remodelling differs between adults with CHD-PAH and PAH from other aetiologies: 3D RV global circumferential strain is better in CHD-PAH patients and associated with survival free from transplant. [ABSTRACT FROM AUTHOR]

Abstract: A solution study on the ability of some derivatised sugars [glucuronic acid (GluA), galacturonic acid (GalA) and glucosaminic acid (GlNA)] to complex the Hg(II) ion is reported. The stability constants of the complex species were determined by potentiometric measurements while 1H NMR experiments allow to define the coordination sites of sugar molecules. GluA coordinates the metal ion through the carboxylic oxygen and the O-4 hydroxyl group and is found to form more stable complexes with respect to GalA in which metal ligation is from the carboxylic oxygen and the O-5 ring oxygen. GlNA forms stable complexes chelating Hg(II) ion through carboxylic oxygen and the α-amino group. The ternary 2,2′-bipyridine containing systems were also investigated by means of potentiometric studies. The ML2 complexes were also isolated in the solid state and characterised by IR spectroscopy. [Copyright &y& Elsevier]

A solution study on the coordinative ability of galactaric acid (GalAH2), d-glucosamine (GlcN) and d-glucosaminic acid (GlcNAH) toward Fe3+ ion is reported. UV spectroscopic study provides useful information to identify complex species formation and their stability constants are determined by means of potentiometric measurements. GalAH2 behaves as chelating ligand through carboxylic oxygen and α-hydroxylic oxygen in the protonated or dissociated form depending on pH value. Two complex species [Fe2GalA(OH)4] and Na[FeGalAH-2] · 2H2O are also isolated in the solid state and characterised through IR spectroscopy. GlcNAH also binds the Fe3+ ion through carboxylic and hydroxylic groups, while NH2 group is probably involved in metal coordiantion up to pH 4. GlcN demonstrates low ligating ability at acidic pH and does not prevent metal hydroxyde precipitation. [Copyright &y& Elsevier]

The aim of this paper is the analysis and examination of the industrial processes for Mozzarella pizza cheese (hereafter referred to as pizza cheese). Specific phases and mechanical devices are studied in order to optimise and rationalise the production cycle. This goal is reached by developing a new and innovative forming method. At present pizza cheese is produced in 1–5 kg pats whereas, as this paper intends to highlight, by forming the cheese in smaller-sized dimensions (5–10 g) the processes will benefit in terms of energy consumption and use of resources (equipment, water, time etc.). Another advantage would be that the customer would be provided with a ready-to-use product, without the need for additional cutting.The paper deals with an innovative process for pizza cheese production, by focusing mainly on the forming phase; a double-screw extruder with a productivity of 20 kg/h was designed and tested in order to evaluate its functionality and applicability.The most relevant spin-offs deriving from the new forming device are the elimination of the pre-hardening phase, the reduction of the chilling time of about 10-fold, the reduction of the total processing time of about 25% and the diminution of the refrigerant water consumption. [Copyright &y& Elsevier]

In 20 patients who had recently had an acute myocardial infarction, we compared endocoronary electrocardiographic modifications recorded during angioplasty with thallium-201 for the detection of myocardial viability. Our data demonstrate that endocoronary electrocardiography can be an easy and reliable tool to assess viability, with sensitivity, specificity, and positive and negative predictive values of 100%, 80%, 94%, 100%, respectively. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) contractile reserve reflects the ability of RV to adapt to elevated afterload. RV functional response to exercise is challenging but could represent an important prognostic factor, especially in pulmonary arterial hypertension (PAH) patients. We aimed, using exercise stress echocardiography (ESE), to assess different RV contractile reserve evaluation methods in a cohort of PAH patients and controls. We prospectively included 12 patients with PAH and 12 healthy volunteers. An ESE (using tilt-table ergometer) was performed in all patients to assess RV function at rest and under peak exercise. Changes in these parameters during exercise were calculated to quantify the RV contractile reserve. 3D RV function as well as peak systolic strain, pulmonary pressures, TAPSE, pulmonary VTI and pulmonary output (using the right ventricular outflow tract diameter) were assessed in all patients. Our patient group was composed by PAH patients, 52 ± 11 years; mean age of our control group was 31 ± 6 years. PAH patients achieved an exercise with a mean workload of 70 ± 26.4 Watts. There was no complication after the exercise test in all patients. Change in TAPSE was not significantly different between patients and controls (P = 0.17), whereas change in pulmonary VTI, pulmonary output and RV peak systolic strain was highly discriminant (respectively P = 0.03, P = 0.009 and P = 0.0009). Regarding RV contractile reserve parameters, RV end-systolic pressure area ratio (peak/rest) was not statistically different between controls and patients (P = 0.14) whereas change in TAPSE/sPAP, RV peak strain/sPAP, 3D RV EF/sPAP were significantly different (P = 0.005, P = 0.0008, P = 0004). Changes in pulmonary output, RV peak systolic strain as well as changes in TAPSE/sPAP but mainly RV peak strain/sPAP, 3D RV EF/sPAP represent consistent and feasible tools to assess RV contractile reserve. [ABSTRACT FROM AUTHOR]

There are ongoing clinical trials on the efficacy of several therapeutic strategies for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among them, the association between hydroxychloroquine (HCQ) and azithromycin (AZT) is under evaluation. Both drugs have a known torsadogenic potential, but QT prolongation induced by this association for inpatient is unknown. To assess QT monitoring of inpatient treated with the association HCQ/AZT for SARS-CoV-2. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for QT analysis (automatic measurement, and Bazett/Fridericia calculation with manual measurement), and after two days of treatment. An institutional protocol (Pasteur University Hospital, Nice) was validated, and allowed HCQ/AZT initiation only if baseline QTc ≥ 480ms and potassium level > 4.0 mmol/L. From March 24th to April 19th, 71 patients were included (mean age 62 ± 14 years, male 66%). Three patients out of 71 (4.2%) were not eligible for drug initiation (QTc ≥ 500ms), and the treatment had to be stopped because of significant QTc prolongation in 2 out of 68 patients (2.9%): concurrent QT-prolonging medication polypharmacy in both patients. Baseline mean QTc was 418 ± 30 ms and lengthened to 442 ± 46 ms after 48 hours of combined therapy (Fig. 1). The agreement coefficient between automatic measurement of QT interval and manual measurements (variability below 5%) was calculated at 57%. A combined therapy, using HCQ/AZT for inpatient SARS-CoV-2, required a close ECG monitoring. This association had to be interrupted in 2.9% of the patients treated. [ABSTRACT FROM AUTHOR]

Active fixation leads for acute complete atrioventricular block (AVB 3) have recently been introduced in the last international guidelines for cardiac pacing. To describe the routine management of acute AVB 3 in France, with emphasis on the organisational aspects. From September 2019 to November 2019, a prospective national survey including 29 questions was electronically sent to 100 physicians (Google Form). The answers were collected from 93 physicians (response rate 93%). A temporary active fixation lead for AVB 3 has already been implanted by 50.5% of the operators. Eighty (86%) have already observed a dislocation of the temporary pacing lead (TPL), a cardiac perforation already occurred in 57 (61.3%), a groin hematoma in 35 (37.6%), and this technique was proscribed for 4.3% of the operators. Definitive pacemaker implantation during weekends and nights (after 8PM) is possible for 48.9% of the operators (< 5 times a year), for 15.2% (> 5 times a year), impossible for 35.9% of the operators. For AVB3 non-responsive to isoproterenol occurring during the night (Fig. 1), a TPL is implanted by: the on-site medical staff on-duty (27.2%), the on-call interventional cardiologist (20.7%), the on-call electrophysiologist (18.5%), a permanent pacemaker is implanted by the electrophysiologist (12%), the strategy is not standardised (15.2%). Our survey shows important disparities in terms of management of acute AVB3 among the different centres, and a high incidence of complications with temporary passive pacing leads. An active fixation lead with an external pacemaker was used by half of the centres. [ABSTRACT FROM AUTHOR]

Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) is a rare inherited channelopathy, responsible for potentially lethal malignant arrhythmic episodes. The index case was a 58-year-old woman who experienced aborted sudden cardiac arrest. The initial complete diagnostic work up (including norepinephrine challenge) was completely negative. She was implanted with an entirely subcutaneous defibrillator. During her follow-up, she received an appropriate electrical shock (ventricular fibrillation). Three sisters had sudden cardiac deaths (SCD) without etiology in the family history. There were no additional reports of pregnancy loss, neonatal death, seizures or SCD in family members. The genetic analysis revealed a Ryanodine Receptor type 2 R4608Q missense variant in this proband. Unfortunately, before the result of the proband's genetic analysis, her daughter experienced a SCD, whilst being implanted with an implantable loop recorder (Fig. 1). A comprehensive genetic analysis was performed in the whole family using Next Generation Sequencing. All the carriers were treated with Nadolol 80 mg per day, and the follow-up was uneventful after six months. A novel Ryanodine Receptor type 2 R4608Q mutation is described in a non-juvenile familial form of CPVT. [ABSTRACT FROM AUTHOR]

Pulmonary embolism (PE) is a common life-threatening disease, with mortality related to right ventricular (RV) dysfunction. Right atrial (RA) dysfunction may be a new marker of PE severity. In this study, we aimed to assess RA function in patients with acute PE, as compared to a control population and to correlate RA function parameters to classic PE severity parameters. We conducted a case-control study, including 27 consecutive PE patients, excluding high-risk PE patients. All patients underwent 2D transthoracic echocardiography with atrial function study within 6 hours of PE diagnosis including RA longitudinal strain (LS) with reservoir (RArLS), conduit (RAcLS) and contractile (RActLS) phases. RA function was assessed using Autostrain LA (TomTec-Philips Medical System). A control group of 18 patients with no structural heart disease in sinus rhythm was recruited in the outpatient clinic. During acute PE, RA strain was impaired in PE patients as compared to controls: P < 0.001 for RAcLS and P = 0.01 for RArLS while no difference in RActLS was observed. When PE severity was graded from 1 to 3 (from intermediate-high to low risk), RAcLS and RArLS were significantly correlated to age and PE severity (Fig. 1). Our RA strain study demonstrates an impaired RA reservoir and conduit function in PE patients, which seems to be related to PE severity. Further studies should help improve our understanding of RA dysfunction in PE. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is a life-threatening condition. Right atrial (RA) dilatation is a prognostic parameter, however, the role of RA and LA function as assessed by speckle-tracking imaging remains unclear. The aim of our study was to assess in PH patients RA and LA function and its relationship with outcomes. Sixty consecutive PH patients [group 1 (72%) and group 4] not eligible to either pulmonary endarterectomy or angioplasty were prospectively enrolled into this echocardiographic cohort study. In addition to clinical assessment, BNP and 6-minute walk test (6MWT), all patients underwent transthoracic echocardiography (TTE) for PH/RV and RA function assessment with 2D speckle-tracking RA longitudinal strain (LS) including reservoir (RArLS), contractile (RActLS) and conduit (RAcLS) phases analysis, LA LS as well as RA and LA volumes and areas. Patients' mean age was 62.8 ± 17.3 years and 57% were female. After a median follow-up of 16 months, 8 patients (13.3%) died. RArLS, RAcLS and RActLS were impaired in patients who died as compared to those who survived (respectively P = 0.003, 0.06 and 0.02). On univariate analysis, BNP, RV end-diastolic diameter, pericardial effusion, mitral lateral E/e', LVEF, TAPSE, LA volume, RA ejection fraction, RActLS, RArLS, RA volume and area were univariate predictors of death or transplant. After multivariable adjustment for age, NYHA class and univariate predictors of death, RA volume (HR = 0.87; 95% CI: 0.78–0.96) and RArLS (HR = 0.007; 95% CI: 0.78–0.96) were independent predictors of outcomes. RA function is an important predictor of outcomes. RA volume and reservoir function appear as independent predictors of death in our cohort. The impairment of RA reservoir function likely represents an early indicator of RV failure, independent of RA dilatation. [ABSTRACT FROM AUTHOR]

Pulmonary arterial hypertension (PAH) is a life-threatening condition. Current ESC guidelines recommend exercise training and rehabilitation in clinically stable PAH patients. To assess the beneficial effect of exercise training on exercise capacity, quality of life and cardiac function as assessed by echocardiography and cardio-pulmonary exercise test. We prospectively included 11 clinically stable PAH patients over a 6-months period. Exercise echocardiography (EE), cardio-pulmonary exercise test (CPET), SF-12quality of life questionnaire, 6-minute walking test (6MWT), BNP and clinical assessment were performed before and after cardio-pulmonary rehabilitation. Patients underwent 8-weeks of exercise training (3 times a week of aerobic training and at home daily prescribed exercises). All patients underwent EE and CPET without any complication. Five patients experienced a reduction in WHO functional class whereas 5 remained stable. Patients significantly improved their physical quality of life (P = 0.006). They also improved their exercise capacity according to the maximum workload during CPET (P = 0.008) and CPET duration (P = 0.001) whereas a trend toward an improved 6MWT was observed (+58 m, P = 0.10). Anaerobic threshold and peak VO2 (+1.7 ± 2.7 mL/kg/min) improved significantly (P = 0.01 and 0.03). Regarding imaging data, at rest, peak strain improved after rehabilitation (P = 0.05) whereas the RV became more dilated. RV contractile reserve, defined by the change in peak systolic longitudinal RV strain between rest and maximum exercise, significantly improved (−3.9 ± 4.7%, P = 0.03). In this preliminary study, cardio-pulmonary rehabilitation led to improved quality of life and exercise capacity in PAH. The increased RV contractile reserve post-rehabilitation might explain, in association with the peripheral muscular effects of exercise training, the clinical benefits of rehabilitation in PAH. [ABSTRACT FROM AUTHOR]

The axillary route use for cardiac devices implantation has recently expanded either with fluoroscopy or ultrasounds guidance. Few studies included defibrillators (ICD), cardiac resynchronization therapy (CRT) and upgrade procedures for ultrasound-guided axillary vein puncture (UGVP). To assess the feasibility/safety of UGVP for complex cardiac devices implantation including CRT/ICD. Consecutive patients eligible for a pacemaker or ICD implantation were included. All procedures were performed by three operators (one experienced and two fellows). Guidewires insertion time (from lidocaïne administration), and complications were systematically studied. A group of patients implanted with alternative techniques was used for comparison (cephalic, subclavian). In 176 consecutive patients in whom UGVP was used, a total of 68 complex procedures were analyzed (74 ± 8 y, male 73%) with 138 leads implanted including 42 ICD, 48 CRT and 16 upgrade procedures. A majority (83%) was under anti-thrombotic therapy. UGAVP was successful in 96.8%. Mean insertion time for 2.02 guidewires per patient was 4.4 ± 4.4 min. Guidewires insertion time reached its plateau after 10 patients. One pocket hematoma (1.4%) was drained during a mean follow-up of 12 ± 5 months. The control group included 24 patients (8 subclavian, 16 cephalic; 15 ICD, 14 CRT, 4 upgrade procedures), with a mean insertion time of 10 ± 8 min, for 1.95 guidewires per patient (P < 0.0005). UGVP is feasible and safe even for complex device implantations including CRT/ICD and upgrade procedures. [ABSTRACT FROM AUTHOR]

Whether unidirectional conduction block (UB) can be observed after creation of a radiofrequency (RF) line is still a subject of debate. Previous study reported a prevalence of 9% of UB, but the assessment was performed using a point-by-point recording across the line, which may have artificially increased this UB percentage. To prospectively assess bidirectional block using ultra-high-resolution (UHR) system after RF line creation. Prospective patients admitted for an RF ablation procedure were included in this study. UHR maps were performed by pacing on both sides of the line created. A total of 18 maps were created in 8 patients (5 men, mean age 71.5 ± 10) by pacing (mean cycle length 600 ± 80 ms) from both sides of the line after a mean waiting time of 60 ± 18 min: 2 left atrial roof and 7 cavotricuspid isthmus lines; mean number of 4863 ± 3982 electrograms (381 ± 651 beats) acquired during 10 ± 9 min; mean right or left atrial volume 81 ± 82 mL. The RF lines were all unambiguously blocked bidirectionally. After a mean follow-up of 12 ± 4 months, no patient experienced any arrhythmia recurrence (Fig. 1). UHR mapping confirmed that the presence of a conduction block along a RF line is always associated with a block in the opposite direction. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common acquired arrhythmia in the intensive care unit (ICU) and is associated with major cardio-vascular complications. However, the association between AF and in-hospital morbi-mortality in ICU remains debated. Furthermore, no prospective study previously assessed long-term outcomes of new-onset AF. To determine the incidence, clinical features, in-hospital and long-term outcomes of new-onset AF in the ICU. We performed a prospective mono-centric observational study. All consecutive patients admitted during a 5-month period were included. Three groups were identified: no AF (No-AF); prior AF (Pr-AF) in case of AF history; and new-onset AF (New-AF) when first AF diagnosis was made during ICU stay. Survivors were followed up during a 6-month period after discharge. We included 110 patients: 23 New-AF, 14 Pr-AF, and 73 No-AF. New-AF were significantly older than No-AF patients. New-AF presented significantly more acute pulmonary oedema and cardiogenic shock than No-AF patients. New-AF was significantly associated with more inotropes or vasopressors use, mechanical ventilation and renal replacement, and had higher in-hospital mortality (43.5% vs. 12%, P = 0.001) than No-AF patients. New-AF had significantly higher levels of troponin and BNP than No-AF patients. At the time of AF occurrence in New-AF group, plasmatic potassium levels were lower than upon admission (3.5 vs. 4.35 mmol/L; P < 0.001). New-AF patients presented significantly more left ventricular systolic and diastolic dysfunction, right ventricular systolic dysfunction and pulmonary arterial hypertension. There was no long-term difference in mortality, heart failure or embolic events between New-AF and No-AF patients. In the ICU, patients with New-onset AF exhibited more cardiogenic and respiratory failure, and had increased in-hospital mortality. No difference in morbi-mortality was observed 6 months after discharge. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) contractile reserve reflects the ability of RV to adapt to elevated afterload. RV functional response to exercise is challenging but could represent an important prognostic factor, especially in pulmonary arterial hypertension (PAH) patients. To assess different RV contractile reserve evaluation methods in a cohort of PAH patients and controls, using exercise stress echocardiography (ESE). We prospectively included 12 patients with PAH and 12 healthy volunteers. An ESE (using tilt-table ergometer) was performed in all patients to assess RV function at rest and under peak exercise. Changes in these parameters during exercise were calculated to quantify the RV contractile reserve. 3D RV function as well as peak systolic strain, pulmonary pressures, TAPSE, pulmonary VTI and pulmonary output (using the right ventricular outflow tract diameter) were assessed in all patients. Our patient group was composed by PAH patients, 52 ± 11 years; mean age of our control group was 31 ± 6 years. PAH patients achieved an exercise with a mean workload of 70 ± 26.4 Watts. There was no complication after the exercise test in all patients. Change in TAPSE was not significantly different between patients and controls (P = 0.17), whereas change in pulmonary VTI, pulmonary output and RV peak systolic strain was highly discriminant (respectively P = 0.03, P = 0.009 and P = 0.0009). Regarding RV contractile reserve parameters, RV end-systolic pressure area ratio (peak/rest) was not statistically different between controls and patients (P = 0.14) whereas change in TAPSE/sPAP, RV peak strain/sPAP, 3D RV EF/sPAP were significantly different (P = 0.005, P = 0.0008, P = 0004). Changes in pulmonary output, RV peak systolic strain as well as changes in TAPSE/sPAP but mainly RV peak strain/sPAP, 3D RV EF/sPAP represent consistent and feasible tools to assess RV contractile reserve. [ABSTRACT FROM AUTHOR]

Outcomes in pulmonary hypertension (PH) are related to right ventricular (RV) function and remodeling. We hypothesized that changes in RV function, especially area strain (AS), could provide incremental prognostic data as compared to baseline data. We aimed to assess RV function changes between baseline and 6-months visit and evaluate their prognostic value in PH using 3D echocardiography. 95 PH patients were prospectively included in this longitudinal study. All patients underwent 2D and 3D transthoracic echocardiography at baseline and 6-month follow-up. 3D RV echocardiographic sequences were analyzed by semi-automatic software and output meshes were post-processed to extract regional deformation. Improvements in the global area strain (lower 2nd measure of area strain) were associated with stable or improving clinical condition as well as survival free from transplant (P < 0.001). The most significant regional changes occurred within the septum. Over a median follow-up of 24.8 months [22.1–25.7], 21 patients died from PH or were transplanted. On multivariate COX analysis, changes in WHO class, BNP and RV global AS were independent predictors of outcomes. Using follow-up data, RV area strain significantly improves the current risk stratification. Changes in RV function and especially follow-up 3D RV AS and RV end-diastolic volume are of prognostic importance. Our study underlines the importance of follow-up data in comparison with baseline data only and demonstrates the additional prognostic value of following changes in RV deformation using 3D echocardiography (Figure 1 , Death or transplant). [ABSTRACT FROM AUTHOR]