Speckle tracking echocardiography in plasma cell disorders: The role of advanced imaging in the early diagnosis of AL systemic cardiac amyloidosis.

INTRODUCTION: Amyloid light-chain amyloidosis is a rare condition characterized by the abnormal production of immunoglobulin light chain that misshape and form amyloid fibrils. Over time, these amyloid deposits can accumulate slowly, causing dysfunction in organs and tissues. Early identification is crucial to ensure optimal treatment. We aim to identify a better marker of cardiac amyloidosis, using advanced echocardiography, to improve diagnosis and the timing of available treatments. MATERIALS AND METHODS: 108 consecutive hematological patients (32, 30% female and 76, 70% male) with a plasma cell disorder referred to our Cardiological center underwent ECG, first and second-level echocardiography (Speckle Tracking) and complete biochemical profile. The best predictors of ALCA (AUC ≥ 0.8) were included in a further analysis stratified by AL score. RESULTS: At ROC analysis, the best bio-humoral predictors for the diagnosis of ALCA were Nt-pro-BNP (AUC: 0.97; p < 0.01) and Hs-Tn (AUC: 0.87; p < 0.01). Regarding echocardiography, the best diagnostic predictors were left atrial stiffness (LAS) (AUC: 0.83; p < 0.01) for the left atrium; free wall thickness for the right ventricle (AUC: 0.82; <0.01); left ventricular global longitudinal strain (LVGLS) (AUC: 0.92; p < 0.01) and LVMi (AUC 0.80; p < 0.001) for the left ventricle; and AL-score (AUC 0.83 p < 0.01). In patients with AL-SCORE < 1, LAS (AUC 0.86 vs AUC 0.79), LVGLS (AUC 0.92 vs AUC 0.86) and LV mass (AUC 0.91 vs AUC 0.72) had better diagnostic accuracy than patients with higher AL-score (AL SCORE ≥ 1). CONCLUSION: Multi-parametric imaging approach with LVGLS and LAS may be helpful for detecting early cardiac involvement in AL amyloidosis.

The role of non-invasive imaging modalities in cardiac allograft vasculopathy: an updated focus on current evidences.

Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy affecting almost 50% of patients after 10 years from heart transplant and represents the most common cause of long-term cardiovascular mortality among heart transplant recipients. The gold standard diagnostic technique is still invasive coronary angiography, which however holds potential for complications, especially contrast-related kidney injury and procedure-related vascular lesions. Non-invasive and contrast-sparing imaging techniques have been advocated and investigated over the past decades, in order to identify those that could replace coronary angiography or at least reach comparable accuracy in CAV detection. In addition, they could help the clinician in defining optimal timing for invasive testing. This review attempts to examine the currently available non-invasive imaging techniques that may be used in the follow-up of heart transplant patients, spanning from echocardiography to nuclear imaging, cardiac magnetic resonance and cardiac computed tomography angiography, weighting their advantages and disadvantages.

Clinical, echocardiographic and hemodynamic predictors of right heart failure after LVAD placement.

Right ventricular failure (RVF) after left ventricular assist device (LVAD) implant is associated with increasing morbidity and mortality. The aim of this study was to identify the best predictors of RVF post LVAD-implant among biochemical, haemodynamic and echocardiographic parameters. From 2009 to 2019, 38 patients who underwent LVAD implantation at our centre were prospectively enrolled. Preoperative clinical, laboratory, echocardiographic and haemodynamic parameters were reported. Overall, eight patients (21%) developed RVF over time, which revealed to be strongly related to overall mortality. Pulmonary artery pulsatility index (PAPi) resulted to be the most significant right heart catheterization index in discriminating RVF vs no RVF patients [(1.32 ± 0.26 vs. 3.95 ± 3.39 respectively) p = 0.0036]. Regarding transthoracic echocardiography, RVF was associated with reduced free wall right ventricular longitudinal strain (fw-RVLS) (- 7.9 ± 1.29 vs. - 16.14 ± 5.83) (p < 0.009), which was superior to other echocardiographic determinants of RVF. Among laboratory values, N-terminal pro-brain natriuretic peptide (NT-proBNP) was strongly increased in RVF patients [(10,496.13 pg/ml ± 5272.96 pg/ml vs. 2865, 5 pg/ml ± 2595.61 pg/ml) p = 0.006]. PAPi, NT-proBNP and fwRVLS were the best pre-operative predictors of RVF, a post-LVAD implant complication which was confirmed to have a great impact on survival. In particular, fwRVLS has been proven to be the strongest independent predictor.

Risk stratification in cardiogenic shock: a focus on the available evidence.

Cardiogenic shock is a clinical syndrome which is defined as the presence of primary cardiac disorder that results in hypotension together with signs of organ hypoperfusion in the state of normovolaemia or hypervolaemia. It represents a complex life-threatening condition, characterized by a high mortality rate, that requires urgent diagnostic assessment as well as treatment; therefore, it is of paramount important to advocate for a thorough risk stratification. In fact, the early identification of patients that could benefit the most from more aggressive and invasive approaches could facilitate a more efficient resource allocation. This review attempts to critically analyse the current evidence on prognosis in cardiogenic shock, focusing in particular on clinical, laboratoristic and echocardiographic prognostic parameters. Furthermore, it focuses also on the available prognostic scores, highlighting the strengths and the possible pitfalls. Finally, it provides insights into future direction that could be followed in order to ameliorate risk stratification in this delicate subset of patients.

Detection of cardiac allograft vasculopathy by multi-layer left ventricular longitudinal strain in heart transplant recipients.

Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse type of coronaropathy that develops in the transplanted human heart, representing a major cause of graft failure and mortality. Nowadays the gold standard for the diagnosis of CAV is coronary angiography (CA). Non-invasive CAV detection, especially in the early stages of the disease, is still challenging. Our study aimed to investigate the role of speckle tracking echocardiography (STE), in particular three-layer STE, in predicting CAV at early stages, and if other traditional echocardiographic, clinical or biochemical parameters could relate to CAV. The study population was composed of a total of 33 heart transplanted patients, divided accordingly to the presence or absence of CAV (12 CAV+ , 22 CAV-). All subjects underwent a complete transthoracic echocardiographic examination on the same day of the CA, and all conventional parameters of myocardial function were obtained, including strain values assessed by STE. Strain values were significantly reduced in presence of CAV, at each myocardial layer but in particular the endocardial-epicardial gradient (- 4.15 ± 1.6 vs - 1.7 ± 0.4% < .0001) that was also highly predictive of CAV (AUC at ROC curve 0.97). Among diastolic parameters, the E wave deceleration time (DT) and the mean E/e' ratio were strongly positively associated with CAV. In our population, left ventricular global longitudinal strain (GLS), layer-specific GLS and the endocardial-epicardial LS gradient, E wave DT and E/e' ratio were the best independent non-invasive predictors of CAV.

Dental identification of unknown bodies through antemortem data taken by non-dental X-rays. Case reports.

The dental radiographic comparison is one of the most reliable and scientifically accepted methods for body identification (ID). The heterogeneity between AM (ante mortem) and PM (postmortem) x-rays images continues to stand as an issue for the forensic odontologist. Casual dental findings on X-rays for investigation of other structures than teeth or maxillaries, could eventually be a relevant source of dental data for the ID especially when AM dental files or X-rays are lacking. Two cases are reported in which the body ID was achieved through the comparison of PM dental X-rays with dental images obtained by radiographies of other structures (e.g. X-rays of the skull or cervical spine). These cases highlight that these occasional dental findings might provide sufficient evidence for a body identification. In the collection of AM data of missing people, the collection of all available records and radiographies of the head, neck and chest should be carefully reviewed by forensic odontologists, seeking for any available dental data.

The tongue protrusion in post-mortem fire.

Burned bodies raise relevant issues for forensic patologist and odontologist both for the identification and the cause of death and possible vital burning.. The tongue protrusion is regularly investigated for the death caused by strangulation or hanging, whilst seems to be overlooked in case of charred remains as the significance of this sign is still discussed. Different mechanims are hypothized in literature to explain the toungue protrusion both for vital and non-vital burning. This paper retrospectively evaluates some cases of carbonized corpses examined at the Forensic Pathology service of the University of Florence. The tongue protrusion shows a high occurrence both in vital (100%) and non-vital fires (66%). The involvement of a forensic odontologist in the cadaver examination result to be limited to one third of the cases. In two non-vital cases the tongue was described as protruded and clenched between the dental arches. The rigor of the genioglossus induced by the heat could explain the phenomenon. Further research on fire fatalities is required to analyze the tongue bleeding as a possible parameter to discriminate the vital by the non-vital tongue protrusion. Moreover, the mechanism at the origin of vital and non-vital tongue protrusion, the different position of the tongue (protruded from an open mouth, protruded and clenched between the dental arches, etc.) in different death circumstances, should be furtherly investigated with a meaningful collaboration between forensic pathologists and odontologists for a complete registration and interpretation of all the mouth originated evidence.

Dental age estimation in children with chromosomal syndromes

When the age of an individual is unknown, age assessment refers to the procedures through which authorities try to establish the chronological age of an individual. Dental evidence demonstrated to be very effective in estimating age and dental mineralization is largely deemed a process scarcely influenced by major diseases and nutritional or environmental factors which can affect child growth. This research aims to understand the possible influence of genetic syndromes on dental maturation of affected individuals. The sample is composed of a test sample of 159 chromosomal affected children, 69 males and 90 females, and a control sample of 157 healthy children, 77 males and 80 females aged between 4,49 and 19,8years. London Atlas was applied to estimate dental age on OPGs (orthopantompographies). No statistical significant difference has been found in dental estimates between syndromic and healthy individuals. Moreover no statistical significant difference emerged between sexes and age cohorts. Children affected by Down or Williams syndromes nor mean error neither the mean accuracy per cohort of age show differences compared to non-affected subjects. The London Atlas can be validly applied to age estimation of individuals with multiple agenesis as in Down and Williams syndromes, even if it a slight overestimation of age occurs systematically in syndromic as well as in healthy samples. The current findings suggest that dental maturation is a very stable biological process scarcely affected by even serious illnesses as genetic syndromes.

The age estimation practice related to illegal unaccompanied minors immigration in Italy.

The migrants arrived to the Italian coasts in 2016 were 181.436, 18% more than the previous year and 6% more than the highest number ever since. An "unaccompanied minor" (UAM) is a third-country national or a stateless person under eighteen years of age, who arrives on the territory of the Member State unaccompanied by an adult responsible for him/her whether by law or by the practice of the Member State concerned, and for as long as he or she is not effectively taken into the care of such a person; it includes a minor who is left unaccompanied after he/she entered the territory of the Member States. As many as 95.985 UAMs applied for international protection in an EU member country just in 2015, almost four times the number registered in the previous year. The UAMs arrived in Italy were 28.283 in 2016; 94% of them were males, 92% unaccompanied, 8% of them under 15; the 53,6% is 17; the individuals between 16 and 17 are instead the 82%. Many of them (50%), 6561 in 2016, escaped from the sanctuaries, thus avoiding to be formally identified and registered in Italy in the attempt to reach more easily northern Europe countries, since The Dublin Regulations (2003) state that the asylum application should be held in the EU country of entrance or where parents reside. The age assessment procedures can therefore be considered as a relevant task that weighs in on the shoulders of the forensic experts with all the related issues and the coming of age is the important threshold. In the EU laws on asylum, the minors are considered as one of the groups of vulnerable persons towards whom Member States have specific obligations. A proper EU common formal regulation in the matter of age estimation procedures still lacks. According to the Italian legal framework in the matter, a medical examination should have been always performed but a new law completely changed the approach to the procedures of age estimation of the migrant (excluding the criminal cases) with a better adherence to the notions and concepts of vulnerability and psychological and social maturity.

Day to day issues in the forensic identification practice related to illegal immigration in Italy.

The migratory flows to Europe from the African countries, Asia and Middle East, have hugely intensified in the recent years. In 2016, more than 98,000 out of a total of 260,000 migrants across the Mediterranean Sea arrived in Italy and in May 2017, the trend of arrivals is: Italy +576%; Greece -39% compared to previous years. Some migrants die before touching the sole of the European continent, during the crossing, often afforded with ships, made available by unscrupulous smugglers or criminal organizations, which are unsuitable for this type of transportation. The tremendous occurrence of migrant casualties during the Mediterranean Sea crossing remains underestimated and nobody, country officers or databank, can provide a reliable number of dead bodies in such a large and now, endemic phenomenon. Forensic officers, who intervened to examine migrants' corpses, are ideally required to perform the usual activity and to answer the routine questions about the causes of death by detecting signs of possible crimes and body identification. In practice, several specific issues and limits challenge the activity of the forensic professionals addressed to ascertain both circumstances of death and possible related crimes and the identity of the corpses. Generally speaking, in case of examining up to a few dead bodies in Italy, a complete autopsy is performed, whilst, when several tens or hundreds of corpses are recovered, the lack of resources on one hand and clearer clues on incident, connected crimes, and cause of deaths on the other, push the public prosecutor to limit the request of complete autopsies. In some cases, the dead migrants were identified through visual recognition by relatives, friends, or travel companions. The DVI Interpol protocol is never completely applied to dead migrants for several reasons, mainly for the huge difficulties in retrieving AM data of the missing persons and for some limitations affecting both the primary and the secondary identifiers. The few chances of identification by dental data are further reduced by the systematic lack of an odontologist among the forensic teams charged of the PM; valuable dental data for body identification or for constructing the biological profile of the missing person (age, ancestry, country of provenance/residence, etc.) are likely to be overlooked. This approach implies a clear disparity with the approach applied when corpses of citizens of the EU or other developed countries are involved and undergo identification. The dead migrants' identification activity should be reconsidered for an improvement in the common international effort in accordance to an approach more respectful toward the legal rights and dignity of the dead migrants and their families.

Newborn screening of inherited metabolic disorders: the Italian situation.

Starting from an international overview of the current status of screening programs, the present paper focuses on the legal situation in Italy and the great differences among Italian regions. Since the introduction of tandem mass spectrometry (MS/MS) in the ‘90s the paradigm “one spot-one disease” changed. Only recently, some regions issued legislative acts to promote expanded newborn screening with MS/MS. This approach raises medico-legal and ethical issues because a fast neonatal diagnosis of an inborn error of metabolism (IEM) could increase chances of an early treatment and reduce disabilities, therefore citizens ought to have the same access to care countrywide. Enacting a mandatory standard for a disease screening panel using MS/MS and a few centers specialized in diagnosis, treatment and follow-up of patients affected by IEM (inborn errors of metabolism) can reduce legal and ethical issues.

First Evidence of Cardiac Stem Cells From the Left Ventricular Apical Tip in Patients With Left Ventricular Assist Device Implantation.

BACKGROUND: Recent studies have challenged the dogma that the adult heart is a postmitotic organ and raise the possibility of the existence of resident cardiac stem cells (CSCs). Our study aimed to explore if these CSCs are present in the "ventricular tip" obtained during left ventricular assist device (LVAD) implantation from patients with end-stage heart failure (HF) and the relationship with LV dysfunctional area extent. METHODS: Four consecutive patients with ischemic cardiomyopathy and end-stage HF submitted to LVAD implantation were studied. The explanted "ventricular tip" was used as a sample of apical myocardial tissue for the pathological examination. Patients underwent clinical and echocardiographic examination, both standard transthoracic echocardiography (TTE) and speckle tracking echocardiography (STE), before LVAD implantation. RESULTS: All patients presented severe apical dysfunction, with apical akinesis/diskinesis and very low levels of apical longitudinal strain (-3.5 ± 2.9%). Despite this, the presence of CSCs was demonstrated in pathological myocardial samples of "ventricular tip" in all 4 of the patients. It was found to be a mean of 6 c-kit cells in 10 fields magnification 40×. CONCLUSIONS: Cardiac stem cells can be identified in the LV apical segment of patients who have undergone LVAD implantation despite LV apical fibrosis.

Multiple deaths caused by a fire in a factory: identification and investigative issues.

The article presents a case of multiple casualties following a textile factory fire. The incident required a full DVI team similar to large mass-disaster because of the specific operational aspects and identification difficulties. The autopsy results were consistent with death by fire and the toxicological investigations revealed carbon monoxide poisoning in four cases (HbCO% ranging between 88,05 and 95,77), two deaths by cyanide intoxication (with concentrations between 5,17 and 8,85 mcg/ml), and in one case there was a synergistic effect of the two substances (carbon monoxide and cyanide). The identification, carried out in accordance with INTERPOL protocols, encountered serious difficulties in the AM phase primarily due to a language barrier and the lack of any dental or medical information relating to the victims. Secondary identifiers proved to be very useful in corroborating possible identities. As a result of the combined efforts of a team of experts the identity of each victim was determined and in all cases at least one primary identifier was used in the identification process. The deployment of DVI teams composed of forensic experts from different fields of expertise and well acquainted with DVI procedures, is essential in events involving multiple casualties that may also include foreign victims. The DVI team should intervene not only in PM examinations but also in the collection of AM data for those individuals not accounted for and by helping police in contacting families of missing people.

Evaluation of Right Ventricular Function in the Management of Patients Referred for Left Ventricular Assist Device Therapy.

BACKGROUND: Speckle tracking echocardiography analysis (STE) has recently allowed an in-depth analysis of right ventricular (RV) performance. The aim of the study was to observe RV function by STE in patients with advanced heart failure before and after left ventricular assist device (LVAD) implantation. METHODS: A transthoracic echocardiogram was performed in 19 patients referred for LVAD implant at baseline and with serial echocardiograms after LVAD implantation (Jarvik 2000). All echocardiographic images were analyzed off line by an independent operator to calculate with STE the RV free wall longitudinal strain (RVLS). RESULTS: All the patients, except 4, showed a progressive increase of RVLS after LVAD implant. However, 4 patients, who presented the lowest RVLS values at baseline, presented a further RV failure in the postoperative. The value of -11% represented the empirical preoperative cutoff able to identify patients at greater risk of postimplant RV failure. CONCLUSIONS: RV myocardial deformation may have important clinical implications for the selection and management of LVAD patients. It can be used to evaluate RV function before LVAD implantation, to drive decisional strategy regarding the management of this type of patients, and after LVAD implant for the follow-up.

HERSCHEL/SCORE, imaging the solar corona in visible and EUV light: CCD camera characterization.

The HERSCHEL (helium resonant scattering in the corona and heliosphere) experiment is a rocket mission that was successfully launched last September from White Sands Missile Range, New Mexico, USA. HERSCHEL was conceived to investigate the solar corona in the extreme UV (EUV) and in the visible broadband polarized brightness and provided, for the first time, a global map of helium in the solar environment. The HERSCHEL payload consisted of a telescope, HERSCHEL EUV Imaging Telescope (HEIT), and two coronagraphs, HECOR (helium coronagraph) and SCORE (sounding coronagraph experiment). The SCORE instrument was designed and developed mainly by Italian research institutes and it is an imaging coronagraph to observe the solar corona from 1.4 to 4 solar radii. SCORE has two detectors for the EUV lines at 121.6 nm (HI) and 30.4 nm (HeII) and the visible broadband polarized brightness. The SCORE UV detector is an intensified CCD with a microchannel plate coupled to a CCD through a fiber-optic bundle. The SCORE visible light detector is a frame-transfer CCD coupled to a polarimeter based on a liquid crystal variable retarder plate. The SCORE coronagraph is described together with the performances of the cameras for imaging the solar corona.

Prognostic value of dipyridamole stress echocardiography in hypertensive patients with left ventricular hypertrophy, chest pain and resting electrocardiographic repolarization abnormalities.

BACKGROUND: Hypertension is a major cardiovascular risk factor in the development of coronary artery disease (CAD); therefore, evaluating the presence of CAD is a primary clinical goal. However, the noninvasive tests that are commonly used have poor diagnostic specificity, particularly in patients with left ventricular hypertrophy. OBJECTIVES: To assess the prognostic value of dipyridamole stress echocardiography (DET) for ischemic events in a subset of patients with hypertension with left ventricular hypertrophy, chest pain and resting electrocardiographic repolarization abnormalities. PATIENTS AND METHODS: Eighty-two patients (48 men and 34 women; average age 65+/-7.2 years with left ventricular hypertrophy documented echocardiographically (left ventricular mass index greater than 50 g/h(2.7)), and resting ST segment shift of 0.1 mV or more from baseline at 80 ms after J point in at least two contiguous leads, were submitted to DET according to high-dosage protocol and coadministered with atropine. RESULTS: The follow-up period was 25.11+/-8.3 months. The stress test produced positive results in 30 patients (36.5%); 16 (53%) and three (5%) cardiac events occurred in positive and negative stress test groups, respectively. At multivariate analysis, only positive DET response (P=0.000002), left ventricular mass index (P=0.028) and a family history of CAD (P=0.037) were independent predictors. The two-year event-free survival rates were 95% and 47% (log-rank 21.093, P=0.00001) for negative and positive stress test results, respectively. CONCLUSIONS: DET is a useful tool in the prognostic assessment of coronary events in this particular subgroup of patients with hypertension.