Publications by authors named "Andrea Rossi"

738 Publications

Multibiomarker responses in Danio rerio after exposure to sediment spiked with triclosan.

An Acad Bras Cienc 2021 20;93(suppl 3):e20201938. Epub 2021 Sep 20.

Universidad Nacional de Luján (UNLu), Grupo de estudios de Contaminación Antrópica en Peces, Instituto de Ecología y Desarrollo Sustentable (CONICET- UNLu), Departamento de Ciencias Básicas, Luján, Ruta 5 y Avenida Constitución, 6700, Buenos Aires, Argentina.

Triclosan (TCS) is an antimicrobial and antimycotic agent widely used in personal care products. In aquatic environments, both TCS and its biomethylated more persistent form, methyl-triclosan (MeTCS), are usually detected in wastewater effluents and rivers, where are commonly adsorbed to suspended solids and sediments. The aim of this study was to evaluate biochemical and physiological effects in Danio rerio after a short term (2 days) and prolonged (21 days) exposures to sediment spiked with TCS acting as the source of the pollutant in the assay. The activities of catalase (CAT), glutathione-s transferase (GST) and superoxide dismutase (SOD), lipid peroxidation levels (LPO), total capacity against peroxyl radicals (ACAP), and acetylcholinesterase enzymatic activity (AChE) were measured in liver, gills, and brain. Most of TCS on the spiked sediment was biotransformed to MeTCS and promoted different adverse effects on D. rerio. Gills were the most sensitive organ after 2 day-exposure, showing lipid damage and increased SOD activity. After 21 days of exposure, liver was the most sensitive organ, showing lower ACAP, increased LPO levels, and SOD and CAT activities. This is the first study reporting the effects on biochemical markers in D. rerio from a MeTCS sink resulting from sediment spiked with TCS.
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http://dx.doi.org/10.1590/0001-3765202120201938DOI Listing
September 2021

L1CAM variants cause two distinct imaging phenotypes on fetal MRI.

Ann Clin Transl Neurol 2021 Sep 12. Epub 2021 Sep 12.

Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Data on fetal MRI in L1 syndrome are scarce with relevant implications for parental counseling and surgical planning. We identified two fetal MR imaging patterns in 10 fetuses harboring L1CAM mutations: the first, observed in 9 fetuses was characterized by callosal anomalies, diencephalosynapsis, and a distinct brainstem malformation with diencephalic-mesencephalic junction dysplasia and brainstem kinking. Cerebellar vermis hypoplasia, aqueductal stenosis, obstructive hydrocephalus, and pontine hypoplasia were variably associated. The second pattern observed in one fetus was characterized by callosal dysgenesis, reduced white matter, and pontine hypoplasia. The identification of these features should alert clinicians to offer a prenatal L1CAM testing.
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http://dx.doi.org/10.1002/acn3.51448DOI Listing
September 2021

Clinical impact of mitral regurgitation in aortic valve stenosis: Insight from effective regurgitant orifice area.

Echocardiography 2021 Sep 9. Epub 2021 Sep 9.

Department of Medicine, Section of Cardiology, University of Verona, Verona, Italy.

Purpose: Mechanisms leading to heart failure (HF) symptoms in aortic valve stenosis (AS) are contentious. We examined the impact of secondary mitral regurgitation (MR) on the symptomatic status in patients with AS.

Methods: Outpatients performing echocardiography with any degree of AS, without organic mitral valve disease, mitral valve intervention, or aortic insufficiency were enrolled. MR was quantitatively defined through mitral effective regurgitant orifice area (EROA) using the proximal isovelocity surface area method. Patients were divided into two groups (New York Heart Association [NYHA] class I-II vs. NYHA class III-IV).

Results: Five hundred and eighty-four patients were enrolled (484 NYHA I-II, 100 NYHA III-IV). More symptomatic patients had smaller aortic valve area (AVA), lower left ventricular ejection fraction (LVEF) and stroke volume, higher E/E', and LV global afterload. MR was present in 178 (30%) patients and EROA was <.20 cm in 158 (89%). NYHA III-IV patients showed higher prevalence of MR (78% vs 21%, P < 0.0001) and larger EROA (.13±.08 cm vs .09±.07 cm , P < 0.0001). An association between EROA and symptoms was present in the total cohort and in subgroups with preserved LVEF, AVA ≥ 1 and <1 cm , EE' 8-14 and ≥14 (P < 0.05 for all). EROA was associated with severe symptoms after adjustment for LVEF, E/E', and AVA in the overall population (OR 1.10 [1.06-1.15]; P < 0.0001) and in the 516 patients with preserved LVEF (OR 1.13 [1.08-1.19]; P < 0.0001).

Conclusion: In patients with AS, greater EROA values are associated with HF symptoms, even though MR degree is far from the threshold of MR severity. Therefore, even a mild MR represents a supportive marker of HF symptoms presence.
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http://dx.doi.org/10.1111/echo.15184DOI Listing
September 2021

The Central Role of Left Atrium in Heart Failure.

Front Cardiovasc Med 2021 13;8:704762. Epub 2021 Aug 13.

Unit of Cardiac Sciences, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.

In past cardiovascular medicine, the attention to the left ventricle-identified as the only indicator and determinant of healthy or unhealthy cardiac conditions- has systematically hidden the role of the left atrium (LA). The recent advances in cardiovascular imaging have provided a better understanding of LA anatomy, physiology, and pathology, making us realize that this functional structure is far from being an innocent spectator. We now know that the LA's mechanical and neuro-hormonal properties play a relevant part in several cardiovascular diseases, including atrial fibrillation, ischemic heart disease, valvular heart disease, and heart failure. The present review aims to describe the role of LA in the specific setting of heart failure. We provide currently available information on LA structure and function and summarize its role as a determinant of symptoms, prognosis, and potential therapeutic target in heart failure patients.
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http://dx.doi.org/10.3389/fcvm.2021.704762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414134PMC
August 2021

External ventricular drainage for posthemorrhagic ventricular dilatation in preterm infants: insights on efficacy and failure.

J Neurosurg Pediatr 2021 Sep 3:1-9. Epub 2021 Sep 3.

1Department Mother and Child, Neonatal Intensive Care Unit, IRCCS Istituto Giannina Gaslini, Genoa.

Objective: The objective of this study was to describe the clinical and neuroradiological characteristics of a cohort of preterm infants who had undergone external ventricular drain insertion as a temporary measure to treat posthemorrhagic ventricular dilatation. In addition, the authors investigated the factors predicting permanent shunt dependency.

Methods: The authors retrospectively reviewed the medical records of a cohort of preterm infants who had undergone external ventricular drain insertion at Gaslini Children's Hospital (Genoa, Italy) between March 2012 and February 2018. They also analyzed clinical characteristics and magnetic resonance imaging data, including diffusion- and susceptibility-weighted imaging studies, which were obtained before both catheter insertion and removal.

Results: Twenty-eight infants were included in the study. The mean gestational age was 28.2 ± 2.7 weeks, and the mean birth weight was 1209 ± 476 g. A permanent ventriculoperitoneal shunt was inserted in 15/28 (53.6%) infants because of the failure of external ventricular drainage as a temporary treatment option. Compared with the shunt-free group, the shunt-dependent group had a significantly lower gestational age (29.3 ± 2.3 vs 27.2 ± 2.7 weeks, p = 0.035) and tended toward a lower birth weight (p = 0.056). None of the clinical and neuroradiological characteristics significantly differed between the shunt-free and shunt-dependent groups at the time of catheter insertion. As expected, ventricular parameters as well as the intraventricular extension of intracerebral hemorrhage, as assessed using the intraventricular hemorrhage score, were reportedly higher in the shunt-dependent group than in the shunt-free group before catheter removal.

Conclusions: External ventricular drainage is a reliable first-line treatment for posthemorrhagic hydrocephalus. However, predicting its efficacy as a unique treatment remains challenging. A lower gestational age is associated with a higher risk of posthemorrhagic hydrocephalus progression, suggesting that the more undeveloped the mechanisms for the clearance of blood degradation products, the greater the risk of requiring permanent cerebrospinal fluid diversion, although sophisticated MRI investigations are currently unable to corroborate this hypothesis.
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http://dx.doi.org/10.3171/2021.5.PEDS20928DOI Listing
September 2021

Metallic, metal oxide, and metalloid nanoparticles toxic effects on freshwater microcrustaceans: an update and basis for the use of new test species.

Water Environ Res 2021 Sep 1. Epub 2021 Sep 1.

Instituto Nacional de Limnología (CONICET-UNL), Ciudad Universitaria, Santa Fe, Argentina.

In this article, we performed a literature review on the metallic, metal oxide, and metalloid nanoparticles (NP) effects on freshwater microcrustaceans, specifically focusing on (i) the main factors influencing the NP toxicity and (ii) their main ecotoxicological effects. Also, given that most studies are currently developed on the standard test species Daphnia magna Straus, we analyzed (iii) the potential differences in the biological responses between D. magna and other freshwater microcrustacean, and (iv) the ecological implications of considering only D. magna as surrogate of other microcrustaceans. We found that NP effects on microcrustaceans depended on their intrinsic properties as well as the exposure conditions. Among the general responses to different NP we identified body burial, feeding inhibition, biochemical effects, metabolic changes, and reproductive and behavioral alterations. The differences in the biological responses between D. magna and other freshwater microcrustacean rely on the morphology (size and shape), ecological traits (feeding mechanisms, life cycles) and intrinsic sensitivities. Thus, we strongly recommend the use of microcrustaceans species with different morphological, physiological, and ecological characteristics in future ecotoxicity tests with NP to provide relevant information with regulation purposes regarding the discharge of NP into aquatic environments.
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http://dx.doi.org/10.1002/wer.1637DOI Listing
September 2021

Determinants of exercise intolerance symptoms considered non-specific for heart failure in patients with stage A and B: role of the left atrium in the transition phase to overt heart failure.

Int J Cardiovasc Imaging 2021 Aug 30. Epub 2021 Aug 30.

Division of Cardiology, Department of Medicine, University Hospital of Verona, University of Verona, P.le Stefani 1, 37126, Verona, Italy.

To assess to what extent left atrial (LA) structure and function are associated with non-specific heart failure symptoms, so that patients were classified as HF stage A and B. Mechanisms underlying the transition to overt HF in patients with stage A and B HF are unclear. Consecutive outpatients undergoing echocardiography and clinical evaluation and classified as HF stage A and B with preserved left ventricular ejection fraction (LVEF) were included. The association between LA measures [volume (LAVi), peak longitudinal-(PALS), contraction-(PACS) and conduit-strain] and non-specific HF symptoms was assessed using adjusted logistic regression analyses. The incremental value of atrial myopathy in symptoms prediction on top of clinical or echocardiographic confounders was assessed through ROC curves analyses. The cohort comprehended 185 patients (63 ± 16 years, 47% women) of whom 133 (72%) were asymptomatic, and 52 (28%) reported non-specific HF symptoms. After adjustment for clinical and echocardiographic confounders for HF symptoms, LAVi, PALS and PACS were associated with symptoms (p < 0.05). Among echocardiographic variables, only LA parameters were significantly associated with symptoms on top of clinical confounders (for LAVi OR [95% CI] 1.56 [1.21-2.00], p < 0.0001; for PALS 1.45 (1.10-1.91), p = 0.0009; for PACS 2.10 [1.33-3.30], p = 0.002). After adjustment for age, hypertension and COPD or E/E', LV mass-i and mitral ERO, atrial myopathy added predictive value for symptoms presence compared to the clinical variables or echocardiographic parameters described (AUC increase 0.80 to 0.88, p = 0.004, and 0.79 to 0.84, p = 0.06, respectively). In patients with HF stages A-B and preserved LVEF, measures of LA structure and function were associated with non-specific HF symptoms. A comprehensive LA remodeling evaluation may help clinicians in the appropriate identification of overt HF.
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http://dx.doi.org/10.1007/s10554-021-02375-0DOI Listing
August 2021

Diagnosis and Management of Aortic Valve Stenosis: The Role of Non-Invasive Imaging.

J Clin Med 2021 Aug 23;10(16). Epub 2021 Aug 23.

Fondazione Poliambulanza, Cardiovascular Disease Unit, Via Leonida Bissolati, 57, 25100 Brescia, Italy.

Aortic stenosis is the most common heart valve disease necessitating surgical or percutaneous intervention. Imaging has a central role for the initial diagnostic work-up, the follow-up and the selection of the optimal timing and type of intervention. Referral for aortic valve replacement is currently driven by the severity and by the presence of aortic stenosis-related symptoms or signs of left ventricular systolic dysfunction. This review aims to provide an update of the imaging techniques and seeks to highlight a practical approach to help clinical decision making.
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http://dx.doi.org/10.3390/jcm10163745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396987PMC
August 2021

Molecular Autopsy of Sudden Cardiac Death in the Genomics Era.

Diagnostics (Basel) 2021 Jul 30;11(8). Epub 2021 Jul 30.

Institute of Life Sciences, Scuola Superiore Sant'Anna, 56124 Pisa, Italy.

Molecular autopsy is the process of investigating sudden death through genetic analysis. It is particularly useful in cases where traditional autopsy is negative or only shows non-diagnostic features, i.e., in sudden unexplained deaths (SUDs), which are often due to an underlying inherited arrhythmogenic cardiac disease. The final goal of molecular autopsy in SUD cases is to aid medico-legal inquiries and to guide cascade genetic screening of the victim's relatives. Early attempts of molecular autopsy relied on Sanger sequencing, which, despite being accurate and easy to use, has a low throughput and can only be employed to analyse a small panel of genes. Conversely, the recent adoption of next-generation sequencing (NGS) technologies has allowed exome/genome wide examination, providing an increase in detection of pathogenic variants and the discovery of newer genotype-phenotype associations. NGS has nonetheless brought new challenges to molecular autopsy, especially regarding the clinical interpretation of the large number of variants of unknown significance detected in each individual.
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http://dx.doi.org/10.3390/diagnostics11081378DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394514PMC
July 2021

Prevalence of obesity and diabetes in older people with sarcopenia defined according to EWGSOP2 and FNHI criteria.

Aging Clin Exp Res 2021 Aug 16. Epub 2021 Aug 16.

Department of Medical Science, University of Ferrara, Via Aldo Moro, 9, 44124, Ferrara, Italy.

Background: Although the prevalence of sarcopenic obesity is increasing, nowadays a universally accepted definition still does not exist. Because, this clinical entity is defined as the combination of obesity and sarcopenia, the diagnosis appears to be strictly linked to criteria used for sarcopenia and the available prevalence data are not uniform. To investigate the prevalence of sarcopenic obesity in older persons according to EWGSOP2 and FNIH criteria. Second, to evaluate the prevalence of diabetes in patients with sarcopenia diagnosed by the two definitions.

Methods: Observational multicenter study performed in 2014 on older patients admitted to 12 Italian hospitals (GLISTEN Study). Data were collected through standardized questionnaires, which assessed: socio-demographic data, cognitive status, functional abilities, pharmacological therapy, comorbidities, and blood tests. Moreover, muscle mass and strength and physical performance were evaluated.

Results: Six hundred and ten were included in the analyses. Among sarcopenic patients, the prevalence of sarcopenic obesity was 30.8% with FNIH and 0% with EWGSOP2 criteria. According to EWGSOP2 criteria, 23.7% of sarcopenic and 30.8% of non-sarcopenic patients were affected by diabetes (p = 0.101); otherwise, using FNIH criteria, 36.3% of sarcopenic and 26.9% of non-sarcopenic patients were diabetic (p = 0.030). After adjustment for potential confounders, diabetic patients had a 73% higher probability of being sarcopenic according to FNIH criteria (OR 1.73; 95% CI 1.13-2.64).

Conclusions: The EWGSOP2 and FNIH sarcopenia criteria are differently related to the prevalence of obesity and diabetes. The EWGSOP2 criteria seem to be not suitable to identify people with sarcopenic obesity.
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http://dx.doi.org/10.1007/s40520-021-01949-1DOI Listing
August 2021

Relationships between subendocardial perfusion impairment, arterial stiffness and orthostatic hypotension in hospitalized elderly individuals.

J Hypertens 2021 Aug 2. Epub 2021 Aug 2.

Section of Geriatric Medicine, Department of Medicine Section of Geriatric Medicine, Department of Surgery, Dentistry, Pediatric and Gynecology, University of Verona, Verona, Italy.

Background: Orthostatic hypotension is an independent risk factor for cardiovascular morbidity and mortality. Arterial stiffness has been shown to be a pathophysiological mechanism linking orthostatic hypotension and increased cardiovascular risk. This study aims to evaluate the relationship between arterial stiffness, orthostatic hypotension and subendocardial viability ratio (SEVR) and moreover to identify the main predictors of orthostatic hypotension, carotid-femoral pulse wave velocity (PWV-cf) and SEVR.

Methods: Seventy-five patients were enrolled (mean age 82.95 ± 6.45) in Verona's AOUI Geriatric ward. They underwent blood pressure, heart rate, body weight measurements and also comorbidity, arterial stiffness (PWV-cf measured by applanation tonometry), SEVR and biochemical indexes.

Results: Prevalence of orthostatic hypotension was 46.6%. Even after adjustment for age, sex, glomerular filtration rate and mean arterial pressure, SEVR values corrected for arterial oxygen and haemoglobin content were statistically lower in orthostatic hypotension patients (P = 0.05) and PWV-cf values were statistically higher in orthostatic hypotension individuals (P = 0.042). In a binary logistic regression, PWV-cf was the only significant predictor of orthostatic hypotension (odds ratio 1.123; P = 0.039; confidence interval = 1.006--1.17).In a backward logistic regression model sex, creatinine clearance and orthostatic hypotension were significant predictors of SEVR corrected for O2 content. Mean arterial pressure, creatinine clearance and orthostatic hypotension were significant predictors of PWV-cf.

Conclusion: This study shows that orthostatic hypotension is related to increased arterial stiffness, confirming its higher prevalence in elderly patients. Orthostatic hypotension was also associated with reduced values of corrected SEVR, showing a relevant consequence of orthostatic hypotension on subendocardial perfusion impairment.
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http://dx.doi.org/10.1097/HJH.0000000000002944DOI Listing
August 2021

Longitudinally Extensive Transverse Myelitis (LETM) and Myopericarditis in a 7-Month-Old Child with SARs-CoV-2 Infection.

Neuropediatrics 2021 Jul 29. Epub 2021 Jul 29.

Unit of Child Neuropsychiatry, Clinical and Surgical Neurosciences Department, IRCCS Giannina Gaslini Institute, Genoa, Genoa, Liguria, Italy.

Introduction:  In the last few months, some pediatric cases with neurological and neuroradiological pictures related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have been reported, often associated with multisystem inflammatory syndrome (MIS-C). The most frequently encountered pediatric neurological complications seem to be postinfectious immune-mediated acute disseminated encephalomyelitis (ADEM)-like changes of the brain, myelitis, neural enhancement, and splenial lesions. Concomitant neurological and cardiac involvement has been reported only in MIS-C, although specific clinical details are often not fully available.

Methods:  In this case report, a very young child infected with SARs-CoV-2 and diagnosed as longitudinal extensive transverse myelitis with concomitant myo-pericarditis is presented.

Results:  A previously healthy 7-month-old girl presented with abrupt onset of generalized weakness with inability to sit up. She had had mild respiratory symptoms 1 week earlier. Spinal magnetic resonance imaging (MRI) showed a T2-hyperintense intramedullary lesion extending from C4 to T2, compatible with acute longitudinally extensive transverse myelitis (LETM). Cerebrospinal fluid analysis was negative.Echocardiography and blood tests were suggestive for myo-pericarditis. Real time polymerase chain reaction for SARS-CoV-2 on nasopharyngeal swab sample tested positive. She was promptly treated with high dose of steroids and immunoglobulin with satisfactory clinical response.

Conclusion:  To the evolving literature of neurological complications of SARs-CoV-2 infection, we add the youngest patient described to date with isolated LETM and concomitant cardiac involvement. Our case suggests that clinicians should be aware of this association, although difficult to recognize in infants. Practitioners are encouraged to consider aggressive first-line immunotherapies with the final aim to prevent permanent disability.
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http://dx.doi.org/10.1055/s-0041-1732364DOI Listing
July 2021

Neurodevelopmental Profile in Children Affected by Ocular Albinism.

Neuropediatrics 2021 Jul 29. Epub 2021 Jul 29.

Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

Aim:  The aim of this study was to detail the neurodevelopmental profile of subjects affected by ocular albinism (OA) and to collect data on GPR143 gene analysis.

Design:  The design of the study involves a retrospective longitudinal observational case series.

Methods:  We collected data on the neurodevelopmental profile of 13 children affected by OA from clinical annual assessments conducted for a period of 6 years after the first evaluation. We described visual profile, neuromotor development and neurological examination, cognitive profile, communication and language skills and behavioral characteristics. The GPR143 gene analysis was performed as well.

Results:  Children presented a variable combination of ocular and oculomotor disorders unchanged during the follow-up, a deficit in visual acuity and in contrast sensitivity that progressively improved. Abnormalities in pattern visual evoked potential were found. No deficits were detected at neurological examination and neuromotor development except for a mild impairment in hand-eye coordination observed in five cases. A language delay was observed in five cases, two of whom had also a developmental quotient delay at 2 years evolving to a borderline/deficit cognitive level at preschool age, difficulties in adaptive behavior and autistic-like features were found. Mutations in the GPR143 gene were identified in the two patients who presented the most severe clinical phenotype.

Conclusion:  Children with OA may share, in addition to a variable combination of ocular signs and symptoms, a neurodevelopment impairment regarding mostly the cognitive, communicative, and social area, especially those with GPR143 mutation.
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http://dx.doi.org/10.1055/s-0041-1732430DOI Listing
July 2021

Aortic valve stenosis burden: Where we are now?

Int J Cardiol 2021 Sep 20;339:128-129. Epub 2021 Jul 20.

Cardiothoracic Department, Fondazione Poliambulanza, Brescia, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2021.07.032DOI Listing
September 2021

Functional Mitral Regurgitation Outcome and Grading in Heart Failure With Reduced Ejection Fraction.

JACC Cardiovasc Imaging 2021 Jul 7. Epub 2021 Jul 7.

Department of Cardiovascular Diseases, Mayo Clinic, Mayo Clinic, Rochester, Minnesota, USA. Electronic address:

Objectives: This study aims to define excess-mortality linked to functional mitral regurgitation (FMR) quantified in routine-practice.

Background: Appraisal of FMR in heart failure with reduced ejection fraction (HFrEF) is challenging because risks of excess mortality remain uncertain and guidelines diverge.

Methods: Cases of HFrEF (ejection-fraction <50%) Stage B-C that were diagnosed between 2003 and 2011 and had routine-practice FMR quantitation (FMR cohort, n = 6,381) were analyzed for excess mortality thresholds/rates within the cohort and in comparison to the general population. These were also compared to those of a degenerative mitral regurgitation (DMR) simultaneous cohort (DMR cohort, n = 2,416).

Results: In the FMR cohort (age: 70 ± 11 years, ejection fraction: 36 ± 10%, effective regurgitant orifice area [EROA]: 0.09 ± 0.13 cm), EROA distribution was skewed towards low-values (≥0.40 cm in only 8% vs 38% for the DMR cohort; P < 0.0001). One-year mortality was high (15.6%), increasing steeply from 13.3% without FMR to 28.5% with EROA ≥0.30 cm (adjusted odds ratio: 1.57 [95% CI: 1.19-2.97]; P = 0.001). In the long term, 3,538 FMR cohort patients died with excess mortality threshold ∼0.10 cm (vs ∼0.20 cm in the DMR cohort), with 0.10 cm EROA increments independently associated with considerable mortality increment (adjusted HR: 1.11 [95% CI: 1.08-1.15]; P < 0.0001) and with no detectable interaction. Compared to the general population, FMR excess mortality increased exponentially with higher EROA (risk ratio point estimates 2.8, 3.8, and 5.1 at EROA 0.20, 0.30, and 0.40 cm, respectively), and was much steeper than that of the DMR cohort (P < 0.0001). In nested models, individualized EROA was the strongest FMR survival marker, and a new expanded FMR grading scale based on 0.10 cm EROA increments provided incremental power over current American Heart Association-American College of Cardiology/European Society of Cardiology guidelines (all P < 0.03).

Conclusions: In HFrEF, FMR is skewed towards smaller EROA. Nevertheless, when measured in routine practice, EROA is the strongest independent FMR determinant of survival after diagnosis. Excess mortality increases exponentially above the threshold of 0.10 cm, with a much steeper slope than in DMR, for any EROA increment. An expanded EROA-based stratification, superior to existing grading schemes in determining survival, should allow guideline harmonization.
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http://dx.doi.org/10.1016/j.jcmg.2021.05.017DOI Listing
July 2021

Generation of an induced pluripotent stem cell line (IUFi001) from a Cockayne syndrome patient carrying a mutation in the ERCC6 gene.

Stem Cell Res 2021 Aug 7;55:102456. Epub 2021 Jul 7.

IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany. Electronic address:

Human fibroblasts from a Cockayne Syndrome (CS) patient carrying the compound heterozygous c.1131 A > T and c.2571C > T within ERCC Excision Repair 6 (ERCC6) were reprogramed to generate integration-free induced pluripotent stem cells (iPSCs). Characterization of IUFi001-iPSCs demonstrated that this iPSC line is free of exogenous reprogrammed genes and maintains the genomic integrity. The pluripotency of IUFi001-iPSCs was confirmed by the expression of the pluripotency-associated markers and by embryoid body-based differentiation into cell types representative of the three germ layers. The generated iPSC line provides a powerful tool to dissect the molecular mechanisms underlying CS caused by mutations within ERCC6.
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http://dx.doi.org/10.1016/j.scr.2021.102456DOI Listing
August 2021

Social cognition in individuals born preterm.

Sci Rep 2021 07 14;11(1):14448. Epub 2021 Jul 14.

Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.

Faces hold a substantial value for effective social interactions and sharing. Covering faces with masks, due to COVID-19 regulations, may lead to difficulties in using social signals, in particular, in individuals with neurodevelopmental conditions. Daily-life social participation of individuals who were born preterm is of immense importance for their quality of life. Here we examined face tuning in individuals (aged 12.79 ± 1.89 years) who were born preterm and exhibited signs of periventricular leukomalacia (PVL), a dominant form of brain injury in preterm birth survivors. For assessing the face sensitivity in this population, we implemented a recently developed experimental tool, a set of Face-n-Food images bordering on the style of Giuseppe Arcimboldo. The key benefit of these images is that single components do not trigger face processing. Although a coarse face schema is thought to be hardwired in the brain, former preterms exhibit substantial shortages in the face tuning not only compared with typically developing controls but also with individuals with autistic spectrum disorders. The lack of correlations between the face sensitivity and other cognitive abilities indicates that these deficits are domain-specific. This underscores impact of preterm birth sequelae for social functioning at large. Comparison of the findings with data in individuals with other neurodevelopmental and neuropsychiatric conditions provides novel insights into the origins of deficient face processing.
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http://dx.doi.org/10.1038/s41598-021-93709-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280144PMC
July 2021

Prognostic interplay of kidney function with sarcopenia, anemia, disability and cognitive impairment. The GLISTEN study.

Eur J Intern Med 2021 Jul 10. Epub 2021 Jul 10.

Department of Geriatrics, Neurosciences and Orthopaedics, Catholic University of the Sacred Heart, Rome, Italy.

Background: Interactions between chronic kidney disease (CKD) and several comorbidities may potentially affect prognosis of older hospitalized patients. This study aims at evaluating the prognostic interactions between estimated glomerular filtration rate (eGFR), anemia, sarcopenia, functional and cognitive dysfunction, and 3-year mortality among older patients discharged from acute care hospitals.

Methods: Our series consisted of 504 older adults enrolled in a multicenter observational study carried out in twelve Acute Geriatric and Internal Medicine wards throughout Italy. CKD was defined as an eGFR< 60 ml/min/1.73 m. Anemia, Short Portable Status Mental Questionnaire (SPMSQ), Basic Activities of Daily Living (BADL), sarcopenia, and Charlson index were considered in the analysis. 3-year survival was investigated by Cox regression and prognostic interactions among study variables were assessed by survival tree analysis. Accuracy of different survival models was investigated by C-index.

Results: eGFR < 30 mL/min/1.73 m, anemia, sarcopenia, SPMSQ ≥ 5, and impairment in 1 or more BADL were significantly associated with mortality. Survival tree analysis showed that patients with eGFR < 35.32 ml/min/1.73 m and SPMSQ ≥ 5 had the highest risk of mortality [hazard ratio (HR): 5.49, 95%CI: 3.04-9.94] followed by those with eGFR < 35.32 ml/min/1.73 m, hemoglobin < 11.95 g/dL and SPMSQ < 5 (HR:3.65; 95%CI: 2.21-6.02) and those with eGFR 35.32-47.99 ml/min/1.73 m and sarcopenia (HR:3.65; 95%CI: 1.99-6.69). Survival tree leaf node membership had good accuracy in predicting the study outcome (C-index: 0.73, 95%CI:0.70-0.76).

Conclusions: Interactions among study risk factors designed distinct risk profiles in older patients discharged from acute care hospitals, that may help identify patients needing targeted interventions and appropriate follow-up after discharge.
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http://dx.doi.org/10.1016/j.ejim.2021.06.031DOI Listing
July 2021

The Contribution of Case Mix, Skill Mix and Care Processes to the Outcomes of Community Hospitals: A Population-Based Observational Study.

Int J Integr Care 2021 Jun 21;21(2):25. Epub 2021 Jun 21.

Department of Biomedical and Neuromotor Sciences, Alma Mater Studiorum, University of Bologna. Via San Giacomo 12, 40126, Bologna, Italy.

Introduction: Community hospitals (CHs) could address the emerging complex care needs of patients. We investigated which characteristics of patients' and CHs affect patient outcomes, in order to identify who could benefit the most from CH care and the best skill mix to deliver this care.

Methods: We analysed all elderly patients discharged from the CHs of Emilia-Romagna, Italy. CH skill mix and care processes were collected with an ad hoc survey. The primary outcome was improvement in the Barthel index (BI) on discharge. Hierarchical regression analysis was performed to test the associations under study.

Results: 53% of the patients had a BI improvement ≥10. After adjusting for the diverse case mix of the patients, no significant association was found between CH characteristics and BI improvement. Patient characteristics explained only a portion of the variability in CH performance.

Discussion: Heterogeneity in case mix reflects the nature of CHs, which play context-specific roles as integrators between primary care services and hospitals. Residual variability in BI improvement rates across CHs might be attributed to aspects of care not detected in our survey.

Conclusions: More research is needed to study the impact of CH skill mix and care processes on patient outcomes.
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http://dx.doi.org/10.5334/ijic.5566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231454PMC
June 2021

Silver Nanoparticle-Based Sensor for the Selective Detection of Nickel Ions.

Nanomaterials (Basel) 2021 Jun 30;11(7). Epub 2021 Jun 30.

School of Biosciences and Veterinary Medicine, University of Camerino, 62032 Camerino, Italy.

Silver nanoparticles (AgNPs) can be used as a surface plasmon resonance (SPR) colorimetric sensor; the correlation between the SPR phenomenon and the aggregation state of nanoparticle allows the real-time detection of a target molecule. Surface functionalization of NPs with proper molecular baits is often performed to establish the selectivity of the sensor. This work reports on the synthesis of AgNPs under reducing conditions and on the functionalization thereof with mercaptoundecanoic acid (11-MUA). UV-VIS Spectroscopy confirmed the formation of AgNPs, eliciting a surface plasmon absorption band (SPAB) at 393 nm that shifted to 417 nm upon surface coating. Dynamic light scattering was used to investigate the surface coatings; moreover, pelleted [email protected] nanoparticles were characterized by scanning electron microscopy (SEM), energy dispersive X-ray analyzers (EDX), and infrared spectroscopy to corroborate the presence of 11MUA on the surface. Most interestingly, the resulting [email protected] selectively detected micromolar levels of Ni, also in the presence of other cations such as Mn, Co, Cd, Cu, Zn, Fe, Hg, Pb, and Cr.
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http://dx.doi.org/10.3390/nano11071733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308118PMC
June 2021

Ecotoxicity of silica nanoparticles in aquatic organisms: An updated review.

Environ Toxicol Pharmacol 2021 Oct 16;87:103689. Epub 2021 Jun 16.

Instituto Nacional de Limnología, CONICET-UNL, Paraje El Pozo, Ciudad Universitaria UNL, Santa Fe, Argentina; Facultad de Humanidades y Ciencias, UNL, Paraje El Pozo, Ciudad Universitaria UNL, Santa Fe, Argentina.

This review aims to (i) provide a current overview of the main characteristics of SiNP (physical and chemical properties, applications, and emissions), (ii) evaluate the scientific production up to date concerning SiNP, with focus on their toxic effects, through a bibliometric analysis, (iii) describe the main toxic mechanisms of SiNP, (iv) assess the current knowledge about ecotoxicity of SiNP on aquatic organisms (marine and freshwater), and (v) identify the main gaps in the knowledge of SiNP toxicity from an environmentally point of view. The scientific production of SiNP concerning their chemical and physical characteristics has increased exponentially. However, little information is available regarding their ecotoxicity. Particle functionalization is a key factor that reduces SiNP toxicity. Most of the studies employed standard species as test organisms, being the local/native ones poorly represented. Further studies employing long-term exposures and environmentally relevant concentrations are needed to deepen the knowledge about this emergent pollutant.
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http://dx.doi.org/10.1016/j.etap.2021.103689DOI Listing
October 2021

Cognitive and White Matter Microstructure Development in Congenital Hypothyroidism and Familial Thyroid Disorders.

J Clin Endocrinol Metab 2021 Jun 9. Epub 2021 Jun 9.

Department of Pediatrics, IRCCS Istituto Giannina Gaslini, Genova, Italy.

Context: Children with congenital hypothyroidism (CH) are at risk for suboptimal neurodevelopment.

Objectives: To evaluate neurocognitive function and white matter microstructure in children with permanent or transient CH and to correlate these findings with disease severity.

Design, Participants And Methods: A retrospective and prospective observational study was conducted in 39 children with permanent or transient CH, and in 39 healthy children. Cognitive function was assessed by Wechsler Intelligence Scale (WISC-IV) and by other tests; the white matter microstructure was investigated by 3 Tesla magnetic resonance (MRI).

Results: Children with permanent CH have lower cognitive scores at a median age of 9.5 years than those with transient CH and controls. An IQ score between 71-84 was found in 28.6% of permanent CH and of <70 (p=0.06) in 10.7%. The Processing Speed Index (PSI, p=0.004), sustained visual attention (p=0.02), reading speed (p=0.0001), written calculations (p=0.002) and numerical knowledge (p=0.0001) were significantly lower than controls. Children born to mothers with Hashimoto's thyroiditis have significantly lower IQ values (p=0.02), Working Memory Index (p=0.03) and PSI (p=0.02). Significantly lower IQ and Verbal Comprehension Index values were found in children with a family history of thyroid disorders (p=0.004; p=0.009), respectively. In children with permanent CH, significant correlations between abnormalities in white matter microstructural, clinical and cognitive measures were documented.

Conclusions: These findings indicate that children with CH are at risk of neurocognitive impairment and white matter abnormalities despite timely and adequate treatment. The association between offspring cognitive vulnerability and maternal thyroid disorders requires careful consideration.
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http://dx.doi.org/10.1210/clinem/dgab412DOI Listing
June 2021

Expanding the clinical and neuroimaging features of post-varicella arteriopathy of childhood.

J Neurol 2021 May 27. Epub 2021 May 27.

Neuroradiology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Objective: Post-varicella arterial ischemic stroke (AIS) is considered an uncommon cause of pediatric stroke that is considered a self-limiting, monophasic disease. However, in a subset of patients, disease recurs; the prevalence of vasculopathy or AIS recurrence, severity of clinical outcomes, and standardized therapies have not been well characterized. Herein, we determined the clinical-neuroradiological features, long-term evolution, and relationship between acute phase treatment and vasculopathy recurrence in a pediatric population with post-varicella AIS.

Methods: Clinical, laboratory, and neuroradiological features of 22 children with post-varicella AIS between 2010 and 2019 (16 males, mean age at stroke 4 years, range 1.7-10) were reviewed. Statistical analyses were performed using χ and Fisher exact tests.

Results: Of the 22 cases, mean time from varicella to stroke was 4.5 months with 3 cases presenting more than 12 months after rash; 21 (95%) were not vaccinated for varicella; 3 (13.6%) had posterior circulation involvement; and 5 (22.7%) had AIS or vasculopathy recurrence, of which 4 recurred 6.1 months to 2.8 years after initial clinical onset. Recurrence was associated with lack of antiviral treatment during the first episode (p = 0.02).

Conclusions: Post-varicella AIS can occur months after rash making diagnosis challenging. Because recurrent vasculopathy was seen predominantly in cases not treated with antiviral therapy during initial presentation, it is important to rapidly diagnose post-varicella AIS through clinical criteria and/or virological testing then treat with antivirals to prevent recurrence.
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http://dx.doi.org/10.1007/s00415-021-10606-6DOI Listing
May 2021

Clinical Evidence in the Treatment of Obstructive Sleep Apnoea with Oral Appliances: A Systematic Review.

Int J Dent 2021 8;2021:6676158. Epub 2021 May 8.

Department of Head and Neck Surgery, Fondazione Policlinico Gemelli IRCCS, Dental Institute, Catholic University of Sacred Heart, Rome, Italy.

Background: Recent clinical guidelines have extended indications for oral appliances to subjects affected by moderate-to-severe obstructive sleep apnoea (OSA). The aim of this systematic review covering this important issue for public health is twofold: updating and summarizing the best available scientific evidence by selecting RCTs of quality only, and identifying the therapeutic pathways that can be transferred to the current clinical practice.

Methods: All the abstracts which were published before February 18, 2019, have been identified in three electronic databases (PubMed, Web of Science, and Cochrane). The Cochrane Collaboration's tool for assessing risk of bias was used as an assessment tool in order to evaluate the quality of the selected studies.

Results: The search strategy yielded 2,260 studies. After removing duplicates and studies that did not comply with the inclusion criteria, 32 full-text articles were assessed for eligibility, and 17 RCTs were finally included in the qualitative synthesis. The 17 selected studies were very heterogeneous in the type of included RCTs in terms of patient inclusion criteria, sample size, distribution of the two genders in the various groups, duration of treatment, and definition of primary and secondary outcomes, without any restriction on the definition of the control group. A common finding was the positive responsiveness of oral appliance treatment in subjects affected by mild-to-moderate OSA with some evidence for cases of severe OSA.

Conclusion: Higher-quality studies are needed in order to provide additional useful guidelines for dental clinicians for OSA management.
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http://dx.doi.org/10.1155/2021/6676158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124002PMC
May 2021

Intermuscular Adipose Tissue as a Risk Factor for Mortality and Muscle Injury in Critically Ill Patients Affected by COVID-19.

Front Physiol 2021 6;12:651167. Epub 2021 May 6.

Department of Anaesthesia and Intensive Care B, University of Verona, Verona, Italy.

Background: Muscular fatigue and injury are frequently observed in critically ill COVID-19 patients. The aim of this study was to determine whether different muscle adipose tissue depots are associated with mortality and muscle damage in patients affected by COVID-19 admitted to the ICU.

Methods: CT images were obtained in 153 ICU patients with COVID-19 (121 males and 32 females). Height, weight, body mass index (BMI), C-reactive protein, Creatine PhosphoKinase (CPK), muscle density, and intermuscular adipose tissue (IMAT) were measured.

Results: Participants in the highest tertile of IMAT/muscle had the shorter 28-day survival from ICU admission as compared to subjects in the first tertile. Estimates derived from the Cox proportional hazard models, after adjustment for age, sex, and BMI, confirmed the results of the survival analysis (HR 3.94, 95% CI: 1.03-15.09). Participants in the lowest tertile of muscle density had the shorter survival at 28 days from ICU admission as compared to subjects in the highest tertile (HR 3.27, 95% CI: 1.18-4.61), but the relationship was no longer significant when age was included in the model. Subjects in the second muscle density tertile did not show an increased risk.Participants in the highest tertile of IMAT/muscle and those in the lowest tertile of muscle density showed both significantly higher CPK adjusted for weight values as evaluated during the first 8 days of hospitalization.

Conclusion: Our data seem to suggest that higher levels of IMAT/muscle and low muscle density are both associated with higher risk of ICU mortality and muscle injury as evaluated with CPK level.
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http://dx.doi.org/10.3389/fphys.2021.651167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134543PMC
May 2021

Biomarkers of exposure and effect in the armoured catfish Hoplosternum littorale during a rice production cycle.

Environ Pollut 2021 Oct 13;287:117356. Epub 2021 May 13.

Instituto Nacional de Limnología (CONICET-UNL), Ciudad Universitaria, 3000, Santa Fe, Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina; Facultad de Humanidades y Ciencias (FHUC-UNL), Ciudad Universitaria, 3000, Santa Fe, Argentina. Electronic address:

Fish cultivation in rice fields is a valuable resource in some rural areas of the world. Fish is a source of protein and an additional source of income for local farmers. However, the use of pesticides may impact fish and consumer health. The aim of this study was to evaluate exposure and effect biomarkers in native fish inhabiting a rice field during a production cycle. Samples of fish, water and sediment from a rice field in Santa Fe, Argentina were collected during a cultivation season (at the beginning: November 2017, in the middle: December 2017 and at the end: February 2018). At each sampling period, fish biomarkers of effect (biometric indices, hematological parameters, energy reserves, oxidative stress and neurotoxicity) were assessed together with pesticide screening in water, sediment, and fish samples. Only herbicides were present in water and sediment samples in agreement with land treatment before rice sowing stage, where only herbicides were applied. In general, the greatest water concentrations of bentazone, glyphosate and aminomethylphosphonic acid (AMPA), and the lowest sediment glyphosate and AMPA levels were observed at the beginning of the farming cycle. Fish bioaccumulated AMPA residues at all sampling periods and showed biological responses to cope with a stressful environment. Alterations in hematological parameters, mobilization of energetic reserves and activation of the antioxidant system were detected. However, no oxidative damage nor neurotoxic effects were present along the production cycle. Under a real exposure scenario, the present work demonstrates that biological changes are induced in fish to cope with stressors present in a rice field. Fish-rice coculture is an efficient and ecologically sustainable approach to increase food supplies, and a better understanding of the effect of this particular environment on fish would allow a greater and safer development of this promising productive activity in South American rice producing countries.
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http://dx.doi.org/10.1016/j.envpol.2021.117356DOI Listing
October 2021

Nosological Differences in the Nature of Punctate White Matter Lesions in Preterm Infants.

Front Neurol 2021 29;12:657461. Epub 2021 Apr 29.

Neonatal Intensive Care Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

The pathogenesis of punctuate white matter lesions (PWMLs), a mild form of white matter damage observed in preterm infants, is still a matter of debate. Susceptibility-weighted imaging (SWI) allows to differentiate PWMLs based on the presence (SWI+) or absence (SWI-) of hemosiderin, but little is known about the significance of this distinction. This retrospective study aimed to compare neuroradiological and clinical characteristics of SWI+ and SWI- PWMLs. MR images of all VLBW infants scanned consecutively at term-equivalent age between April 2012 and May 2018 were retrospectively reviewed, and infants with PWMLs defined as small areas of high T1 and/or low T2 signal in the periventricular white matter were selected and included in the study. Each lesion was analyzed separately and characterized by localization, organization pattern, and distance from the lateral ventricle. Clinical data were retrieved from the department database. A total of 517 PWMLs were registered in 81 patients, with 93 lesions (18%) visible on SWI (SWI+), revealing the presence of hemosiderin deposits. On univariate analysis, compared to SWI- PWML, SWI+ lesions were closer to the ventricle wall, more frequently organized in linear pattern and associated with lower birth weight, lower gestational age, lower admission temperature, need for intubation, bronchopulmonary dysplasia, retinopathy of prematurity, and presence of GMH-IVH. On multivariate analysis, closer distance to the ventricle wall on axial scan and lower birth weight were associated with visibility of PMWLs on SWI ( = 0.003 and = 0.0001, respectively). Our results suggest a nosological difference between SWI+ and SWI- PWMLs. Other prospective studies are warranted to corroborate these observations.
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http://dx.doi.org/10.3389/fneur.2021.657461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117674PMC
April 2021

Knee flexor and extensor torque ratio in elderly men and women with and without obesity: a cross-sectional study.

Aging Clin Exp Res 2021 May 15. Epub 2021 May 15.

Department of Medicine, Section of Geriatrics, Healthy Aging Center Verona, Verona, Italy.

Background: With aging and obesity lower limb torque deteriorates. Importantly, the ratio between knee flexor (KF) and extensor (KE) torque is an indicator of joint stability.

Aims: We compared KF torque and KF/KE ratio in older subjects of both sexes with obesity (OB) or without (NOB) obesity.

Methods: The maximal torque during KE and KF isokinetic contractions were evaluated at: 60, 90, 150, 180 and 210 deg/s in 89 elderly (68 ± 5 years) subjects with NOB (BMI < 30 kg/m) and OB (BMI ≥ 30 kg/m). Values were normalised for body weight (BW) and leg lean mass (i.e., muscle quality).

Results: At all speeds men had higher absolute KF values (P < 0.001). When values were normalised for BW, sex differences remain in favour of men (P < 0.001) with lower values in both groups with OB than NOB (P < 0.001). Muscle quality and KF/KE ratio were lower in OB than NOB (P < 0.001).

Conclusions: The KF torque and KF/KE ratio decline with aging and with OB. In all groups, the KF/KE ratio was below the joint stability threshold. Thus, exercise physiologists should include exercises designed to train both KE and KF in older subjects with OB.
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http://dx.doi.org/10.1007/s40520-021-01884-1DOI Listing
May 2021

Prolonged care delivery time and reduced rate of electrophysiological procedures during the lockdown period due to Covid-19 outbreak.

Expert Rev Med Devices 2021 May 24;18(5):493-498. Epub 2021 May 24.

Cardiology and Electrophysiology Unit, S. Maria Nuova Hospital, Florence, Italy.

Objectives: The aim of this study is to demonstrate how Electrophysiology activity has been impacted by the pandemic Coronavirus disease 2019 (COVID-19).

Methods: In this multicenter retrospective study, we analyze all consecutive patients admitted for electrophysiological procedures during the COVID-19 lockdown in the Tuscany region of Italy, comparing them to patients hospitalized in the corresponding period of the previous year.

Results: The impact of COVID-19 on cardiac arrhythmia management was impressive, with a reduction of more than 50% in all kinds of procedures. A gender gap was observed, with a more relevant reduction for female patients. Arrhythmic urgencies requiring a device implant showed a reduced time from symptoms to first medical contact but the time from first medical contact to procedure was significantly prolonged.

Conclusion: Hospitals need to consider how outbreaks may affect health systems beyond the immediate infection. Routine activity should be based on a risk assessment between the prompt performance of procedure and its postponement. Retrospective observational analysis such as this study could be decisive in evidence-based medicine of any future pathogen outbreak.Nonstandard Abbreviations and Acronyms PM= pacemakerICD= implantable cardioverter defibrillatorECV= electrical cardioversionEPS= electrophysiological studyAP= ablations proceduresCIED= cardiac implantable electronic devicesWCD= wearable cardioverter defibrillatorEP Lab= Electrophysiology LaboratoriesAVNRT =atrioventricular nodal reentry tachycardiaAVRT= atrioventricular reentry tachycardiaAFL= atrial flutterAF= atrial fibrillationVT= ventricular tachycardiaAT= atrial tachycardia.
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http://dx.doi.org/10.1080/17434440.2021.1926985DOI Listing
May 2021
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