Contemporary Advances in Cardiac Remote Monitoring: A Comprehensive, Updated Mini-Review.

Over the past decade, remote monitoring (RM) has become an increasingly popular way to improve healthcare and health outcomes. Modern cardiac implantable electronic devices (CIEDs) are capable of recording an increasing amount of data related to CIED function, arrhythmias, physiological status and hemodynamic parameters, providing in-depth and updated information on patient cardiovascular function. The extensive use of RM for patients with CIED allows for early diagnosis and rapid assessment of relevant issues, both clinical and technical, as well as replacing outpatient follow-up improving overall management without compromise safety. This approach is recommended by current guidelines for all eligible patients affected by different chronic cardiac conditions including either brady- and tachy-arrhythmias and heart failure. Beyond to clinical advantages, RM has demonstrated cost-effectiveness and is associated with elevated levels of patient satisfaction. Future perspectives include improving security, interoperability and diagnostic power as well as to engage patients with digital health technology. This review aims to update existing data concerning clinical outcomes in patients managed with RM in the wide spectrum of cardiac arrhythmias and Hear Failure (HF), disclosing also about safety, effectiveness, patient satisfaction and cost-saving.

Resection to restoration: Assessing the synergy of polypropylene mesh (Marlex®) combined with methyl-methacrylate and latissimus dorsi flap for primary chest wall sarcomas.

BACKGROUND: Chest-wall sarcomas are treated with extensive resections and complex defect reconstruction to restore chest-wall integrity. It is a difficult surgical procedure that incorporates a multidisciplinary approach for the best outcome, preventing paradoxical chest movement issues and reducing complications. OBJECTIVE: We aimed to describe our experience of chest-wall reconstruction using polypropylene mesh (Marlex® Mesh) combined with methyl-methacrylate and soft-tissue coverage with a latissimus dorsi flap following sarcoma resection. PATIENTS AND METHODS: Among the 53 patients treated for primary chest-wall sarcomas at the European Institute of Oncology (IEO) in Milan, Italy, from 1998 to 2020, 14 cases underwent chest-wall resection and reconstruction using polypropylene mesh, methyl-methacrylate and the latissimus dorsi flap. Patients with locally advanced breast cancers, locally advanced lung cancers, squamous cell carcinomas, and other secondary chest-wall malignancies were excluded from the study, as were the patients with different types of chest-wall reconstruction. RESULTS: In this study, 14 patients (6 men and 8 women) with various primary chest-wall sarcomas were enrolled. On an average, 2 ribs (range: 1-5) were removed during the surgeries, and the chest-wall defects ranged from 20 to 150 cm2 with an average size of 73 cm2. The mean follow-up period for these patients was approximately 63.80 months CONCLUSION: The combination of Marlex® mesh filled with methyl-methacrylate and covered using latissimus dorsi myocutaneous flap provides safe, low-cost and effective single-stage chest-wall reconstruction after surgery for primary sarcomas.

Laboratory investigation of peritoneal fluids: an updated practical approach based on the available evidence.

Even though analysis of peritoneal fluids (PF) is often requested to medical laboratories for biochemical and morphological tests, there is still no mutual agreement on what the most appropriate way is to manage PF samples and which tests should be appropriately executed. In this update, we tried to identify the most useful tests for PF analysis to establish best practice indications. We performed a literature review and examined available guidelines to select the most appropriate tests by an evidence-based approach. Accordingly, the basic PF profile should include (1) serum to effusion albumin gradient and (2) automated cell counts with differential analysis. This profile allows to determine the PF nature, differentiating between 'high-albumin gradient' and 'low-albumin gradient' effusions, which helps to identify the pathophysiological process causing the ascites formation. Restricted to specific clinical situations, additional tests can be requested as follows: PF lactate dehydrogenase (LDH) and glucose, to exclude (LDH) or confirm (glucose) secondary bacterial peritonitis; PF total protein, to differentiate ascites of cardiac origin from other causes; PF (pancreatic) amylase, for the identification of pancreatic ascites; PF bilirubin, when a choleperitoneum is suspected; PF triglycerides, in differentiating chylous from pseudochylous ascites and PF creatinine, to detect intraperitoneal urinary leakage.

Arrhythmogenic Cardiomyopathy: Definition, Classification and Arrhythmic Risk Stratification.

Arrhythmogenic cardiomyopathy (ACM) is a heart disease characterized by a fibrotic replacement of myocardial tissue and a consequent predisposition to ventricular arrhythmic events, especially in the young. Post-mortem studies and the subsequent diffusion of cardiac MRI have shown that left ventricular involvement in arrhythmogenic cardiomyopathy is common and often develops early. Regarding the arrhythmic risk stratification, the current scores underestimate the arrhythmic risk of patients with arrhythmogenic cardiomyopathy with left involvement. Indeed, the data on arrhythmic risk stratification in this group of patients are contradictory and not exhaustive, with the consequence of not correctly identifying patients at a high arrhythmic risk who deserve protection from arrhythmic death. We propose a literature review on arrhythmic risk stratification in patients with ACM and left involvement to identify the main features associated with an increased arrhythmic risk in this group of patients.

The Fluoroless Future in Electrophysiology: A State-of-the-Art Review.

Fluoroscopy has always been the cornerstone imaging method of interventional cardiology procedures. However, radiation exposure is linked to an increased risk of malignancies and multiorgan diseases. The medical team is even more exposed to X-rays, and a higher incidence of malignancies was reported in this professional group. In the last years, X-ray exposure has increased rapidly, involving, above all, the medical team and young patients and forcing alternative fluoroless imaging methods. In cardiac electrophysiology (EP) and pacing, the advent of 3D electroanatomic mapping systems with dedicated catheters has allowed real-time, high-density reconstruction of both heart anatomy and electrical activity, significantly reducing the use of fluoroscopy. In addition, the diffusion of intracardiac echocardiography has provided high anatomical resolution of moving cardiac structures, providing intraprocedural guidance for more complex catheter ablation procedures. These methods have largely demonstrated safety and effectiveness, allowing for a dramatic reduction in X-ray delivery in most arrhythmias' ablations. However, some technical concerns, as well as higher costs, currently do not allow their spread out in EP labs and limit their use to only procedures that are considered highly complex and time-consuming and in young patients. In this review, we aim to update the current employment of fluoroless imaging in different EP procedures, focusing on its strengths and weaknesses.

Validation of metrological traceability of the new generation of Abbott Alinity alkaline phosphatase assay.

OBJECTIVES: Recently, Abbott Diagnostics marketed a new generation of Alinity enzyme assays, introducing a multiparametric calibrator [Consolidated Chemistry Calibrator (ConCC)] in place of or in addition to factor-based calibrations. For alkaline phosphatase (ALP), both calibration options are offered, i.e., with ConCC (ALP2) and with an experimental calibration factor (ALP2F). Both options are declared traceable to the 2011 IFCC reference measurement procedure (RMP). Before to replace the old generation (ALP1) with the new one, we decided to validate the trueness of ALP2/ALP2F. METHODS: Three approaches were employed: (a) preliminary comparison on 48 native frozen serum samples with ALP1, of which traceability to RMP was previously successfully verified; (b) examination of three banked serum pools (BSP) with values assigned by RMP; (c) direct comparison with RMP on a set of 24 fresh serum samples. Bias estimation and regression studies were performed, and the standard measurement uncertainty associated with ALP measurements on clinical samples (uresult) was estimated and compared with established analytical performance specifications (APS). ConCC commutability was also assessed. RESULTS: A positive proportional bias was found with both ALP2 and ALP2F when compared to ALP1 and RMP. This positive bias was confirmed on BSP: in average, +13.1 % for ALP2 and +10.0 % for ALP2F, respectively. uresult were 13.28 % for ALP2 and 10.04 % for ALP2F, both not fulfilling the minimum APS of 4.0 %. Furthermore, ConCC was not commutable with clinical samples. CONCLUSIONS: Our results unearth problems in the correct implementation of traceability of Alinity ALP2/ALP2F, with the risk for the new assay to be unfit for clinical purposes.

How to recognize pulmonary embolism in syncope patients: A simple rule.

BACKGROUND: Syncope can be the presenting symptom of Pulmonary Embolism (PE). It is not known wether using a standardized algorithm to rule-out PE in all patients with syncope admitted to the Emergency Departments (ED) is of value or can lead to overdiagnosis and overtreatment. METHODS: We tested if simple anamnestic and clinical parameters could be used as a rule to identify patients with syncope and PE in a multicenter observational study. The rule's sensitivity was tested on a cohort of patients that presented to the ED for syncopal episodes caused by PE. The clinical impact of the rule was assessed on a population of consecutive patients admitted for syncope in the ED. RESULTS: Patients were considered rule-positive in the presence of any of the following: hypotension, tachycardia, peripheral oxygen saturation ≤ 93 % (SpO2), chest pain, dyspnea, recent history of prolonged bed rest, clinical signs of deep vein thrombosis, history of previous venous thrombo-embolism and active neoplastic disease. The sensitivity of the rule was 90.3 % (95 % CI: 74.3 % to 98.0 %). The application of the rule to a population of 217 patients with syncope would have led to a 70 % reduction in the number of subjects needing additional diagnostic tests to exclude PE. CONCLUSIONS: Most patients with syncope due to PE present with anamnestic and clinical features indicative of PE diagnosis. A clinical decision rule can be used to identify patients who would benefit from further diagnostic tests to exclude PE, while reducing unnecessary exams that could lead to over-testing and over-diagnosis.

Inactivation of hypocretin receptor-2 signaling in dopaminergic neurons induces hyperarousal and enhanced cognition but impaired inhibitory control.

Hypocretin/Orexin (HCRT/OX) and dopamine (DA) are both key effectors of salience processing, reward and stress-related behaviors and motivational states, yet their respective roles and interactions are poorly delineated. We inactivated HCRT-to-DA connectivity by genetic disruption of Hypocretin receptor-1 (Hcrtr1), Hypocretin receptor-2 (Hcrtr2), or both receptors (Hcrtr1&2) in DA neurons and analyzed the consequences on vigilance states, brain oscillations and cognitive performance in freely behaving mice. Unexpectedly, loss of Hcrtr2, but not Hcrtr1 or Hcrtr1&2, induced a dramatic increase in theta (7-11 Hz) electroencephalographic (EEG) activity in both wakefulness and rapid-eye-movement sleep (REMS). DAHcrtr2-deficient mice spent more time in an active (or theta activity-enriched) substate of wakefulness, and exhibited prolonged REMS. Additionally, both wake and REMS displayed enhanced theta-gamma phase-amplitude coupling. The baseline waking EEG of DAHcrtr2-deficient mice exhibited diminished infra-theta, but increased theta power, two hallmarks of EEG hyperarousal, that were however uncoupled from locomotor activity. Upon exposure to novel, either rewarding or stress-inducing environments, DAHcrtr2-deficient mice featured more pronounced waking theta and fast-gamma (52-80 Hz) EEG activity surges compared to littermate controls, further suggesting increased alertness. Cognitive performance was evaluated in an operant conditioning paradigm, which revealed that DAHcrtr2-ablated mice manifest faster task acquisition and higher choice accuracy under increasingly demanding task contingencies. However, the mice concurrently displayed maladaptive patterns of reward-seeking, with behavioral indices of enhanced impulsivity and compulsivity. None of the EEG changes observed in DAHcrtr2-deficient mice were seen in DAHcrtr1-ablated mice, which tended to show opposite EEG phenotypes. Our findings establish a clear genetically-defined link between monosynaptic HCRT-to-DA neurotransmission and theta oscillations, with a differential and novel role of HCRTR2 in theta-gamma cross-frequency coupling, attentional processes, and executive functions, relevant to disorders including narcolepsy, attention-deficit/hyperactivity disorder, and Parkinson's disease.

The genomic echoes of the last Green Sahara on the Fulani and Sahelian people.

The population history of the Sahara/Sahelian belt is understudied, despite previous work highlighting complex dynamics.1,2,3,4,5,6,7 The Sahelian Fulani, i.e., the largest nomadic pastoral population in the world,8 represent an interesting case because they show a non-negligible proportion of an Eurasian genetic component, usually explained by recent admixture with northern Africans.1,2,5,6,7,9,10,11,12 Nevertheless, their origins are largely unknown, although several hypotheses have been proposed, including a possible link to ancient peoples settled in the Sahara during its last humid phase (Green Sahara, 12,000-5,000 years before present [BP]).13,14,15 To shed light about the Fulani ancient genetic roots, we produced 23 high-coverage (30×) whole genomes from Fulani individuals from 8 Sahelian countries, plus 17 samples from other African groups and 3 from Europeans as controls, for a total of 43 new whole genomes. These data have been compared with 814 published modern whole genomes2,16,17,18 and with relevant published ancient sequences (> 1,800 samples).19 These analyses showed some evidence that the non-sub-Saharan genetic ancestry component of the Fulani might have also been shaped by older events,1,5,6 possibly tracing the Fulani origins to unsampled ancient Green Saharan population(s). The joint analysis of modern and ancient samples allowed us to shed light on the genetic ancestry composition of such ancient Saharans, suggesting a similarity with Late Neolithic Moroccans and possibly pointing to a link with the spread of cattle herding. We also identified two different Fulani clusters whose admixture pattern may be informative about the historical Fulani movements and their later involvement in the western African empires.

Global genetic diversity, introgression, and evolutionary adaptation of indicine cattle revealed by whole genome sequencing.

Indicine cattle, also referred to as zebu (Bos taurus indicus), play a central role in pastoral communities across a wide range of agro-ecosystems, from extremely hot semiarid regions to hot humid tropical regions. However, their adaptive genetic changes following their dispersal into East Asia from the Indian subcontinent have remained poorly documented. Here, we characterize their global genetic diversity using high-quality whole-genome sequencing data from 354 indicine cattle of 57 breeds/populations, including major indicine phylogeographic groups worldwide. We reveal their probable migration into East Asia was along a coastal route rather than inland routes and we detected introgression from other bovine species. Genomic regions carrying morphology-, immune-, and heat-tolerance-related genes underwent divergent selection according to Asian agro-ecologies. We identify distinct sets of loci that contain promising candidate variants for adaptation to hot semi-arid and hot humid tropical ecosystems. Our results indicate that the rapid and successful adaptation of East Asian indicine cattle to hot humid environments was promoted by localized introgression from banteng and/or gaur. Our findings provide insights into the history and environmental adaptation of indicine cattle.

Fighting Cardiac Thromboembolism during Transcatheter Procedures: An Update on the Use of Cerebral Protection Devices in Cath Labs and EP Labs.

Intraprocedural stroke is a well-documented and feared potential risk of cardiovascular transcatheter procedures (TPs). Moreover, subclinical neurological events or covert central nervous system infarctions are concerns related to the development of dementia, future stroke, cognitive decline, and increased risk of mortality. Cerebral protection devices (CPDs) were developed to mitigate the risk of cardioembolic embolism during TPs. They are mechanical barriers designed to cover the ostium of the supra-aortic branches in the aortic arch, but newer devices are able to protect the descending aorta. CPDs have been mainly designed and tested to provide cerebral protection during transcatheter aortic valve replacement (TAVR), but their use in both Catheterization and Electrophysiology laboratories is rapidly increasing. CPDs have allowed us to perform procedures that were previously contraindicated due to high thromboembolic risk, such as in cases of intracardiac thrombosis identified at preprocedural assessment. However, several concerns related to their employment have to be defined. The selection of patients at high risk of thromboembolism is still a subjective choice of each center. The aim of this review is to update the evidence on the use of CPDs in either Cath labs or EP labs, providing an overview of their structural characteristics. Future perspectives focusing on their possible future employment are also discussed.

C-reactive protein and clinical outcome in COVID-19 patients: the importance of harmonized measurements.

C-reactive protein (CRP) is a cytokine-mediated acute phase reactant with a recognized role in inflammatory conditions and infectious disease. In coronavirus disease 2019 (COVID-19), elevated CRP concentrations in serum were frequently detected and significantly associated with poor outcome in terms of disease severity, need for intensive care, and in-hospital death. For these reasons, the marker was proposed as a powerful test for prognostic classification of COVID-19 patients. In most of available publications, there was however confounding information about how interpretative criteria for CRP in COVID-19 should be derived, including quality of employed assays and optimal cut-off definition. Assuring result harmonization and controlling measurement uncertainty in terms of performance specifications are fundamental to allow worldwide application of clinical information according to specific CRP thresholds and to avoid risk of patient misclassification.

The worldwide spread of Aedes albopictus: New insights from mitogenomes.

The tiger mosquito (Aedes albopictus) is one of the most invasive species in the world and a competent vector for numerous arboviruses, thus the study and monitoring of its fast worldwide spread is crucial for global public health. The small extra-nuclear and maternally-inherited mitochondrial DNA represents a key tool for reconstructing phylogenetic and phylogeographic relationships within a species, especially when analyzed at the mitogenome level. Here the mitogenome variation of 76 tiger mosquitoes, 37 of which new and collected from both wild adventive populations and laboratory strains, was investigated. This analysis significantly improved the global mtDNA phylogeny of Ae. albopictus, uncovering new branches and sub-branches within haplogroup A1, the one involved in its recent worldwide spread. Our phylogeographic approach shows that the current distribution of tiger mosquito mitogenome variation has been strongly affected by clonal and sub-clonal founder events, sometimes involving wide geographic areas, even across continents, thus shedding light on the Asian sources of worldwide adventive populations. In particular, different starting points for the two major clades within A1 are suggested, with A1a spreading mainly along temperate areas from Japanese and Chinese sources, and A1b arising and mainly diffusing in tropical areas from a South Asian source.

The ß2V287L nicotinic subunit linked to sleep-related epilepsy differently affects fast-spiking and regular spiking somatostatin-expressing neurons in murine prefrontal cortex.

Mutant subunits of the neuronal nicotinic ACh receptor (nAChR) can cause Autosomal Dominant Sleep-related Hypermotor Epilepsy (ADSHE), characterized by frontal seizures during non-rapid eye movement (NREM) sleep. We studied the cellular bases of the pathogenesis in brain slices from mice conditionally expressing the ADSHE-linked ß2V287L nAChR subunit. ß2V287L mice displayed minor structural alterations, except for a ~10% decrease of prefrontal cortex thickness. However, they showed a substantial decrease of the excitatory input to layer V fast-spiking (FS) interneurons, despite a concomitant increase in the number of glutamatergic terminals around the cell soma. Hence, prefrontal hyperexcitability may depend on a permanent impairment of surround inhibition. The effect disappeared when ß2V287L was silenced until postnatal day 15th, suggesting that the transgene selectively affects the maturation of glutamatergic synapses on FS neurons. The other main population of interneurons in layer V was constituted by somatostatin-expressing regular spiking cells. When tested with 10 µM nicotine, these displayed larger somatic nicotinic currents in transgenic mice. Thus, during wakefulness, activation of ß2V287L-containing nAChRs by the high cholinergic tone may counteract hyperexcitability by promoting local inhibition by somatostatin-expressing cells and decreasing the effect of glutamatergic deficit in FS neurons. This interpretation was tested in networks disinhibited by 2 µM bicuculline. Slices expressing ß2V287L were more susceptible to develop synchronized activity in the absence of nicotine. Addition of the drug boosted excitability in the controls, but had little effect in ß2V287L. Our findings suggest why NREM sleep favors ADSHE seizures and nicotine can be palliative in patients.

The Mitogenome Relationships and Phylogeography of Barn Swallows (Hirundo rustica).

The barn swallow (Hirundo rustica) poses a number of fascinating scientific questions, including the taxonomic status of postulated subspecies. Here, we obtained and assessed the sequence variation of 411 complete mitogenomes, mainly from the European H. r. rustica, but other subspecies as well. In almost every case, we observed subspecies-specific haplogroups, which we employed together with estimated radiation times to postulate a model for the geographical and temporal worldwide spread of the species. The female barn swallow carrying the Hirundo rustica ancestral mitogenome left Africa (or its vicinity) around 280 thousand years ago (kya), and her descendants expanded first into Eurasia and then, at least 51 kya, into the Americas, from where a relatively recent (<20 kya) back migration to Asia took place. The exception to the haplogroup subspecies specificity is represented by the sedentary Levantine H. r. transitiva that extensively shares haplogroup A with the migratory European H. r. rustica and, to a lesser extent, haplogroup B with the Egyptian H. r. savignii. Our data indicate that rustica and transitiva most likely derive from a sedentary Levantine population source that split at the end of the Younger Dryas (YD) (11.7 kya). Since then, however, transitiva received genetic inputs from and admixed with both the closely related rustica and the adjacent savignii. Demographic analyses confirm this species' strong link with climate fluctuations and human activities making it an excellent indicator for monitoring and assessing the impact of current global changes on wildlife.

Overview of the Americas' First Peopling from a Patrilineal Perspective: New Evidence from the Southern Continent.

Uniparental genetic systems are unique sex indicators and complement the study of autosomal diversity by providing landmarks of human migrations that repeatedly shaped the structure of extant populations. Our knowledge of the variation of the male-specific region of the Y chromosome in Native Americans is still rather scarce and scattered, but by merging sequence information from modern and ancient individuals, we here provide a comprehensive and updated phylogeny of the distinctive Native American branches of haplogroups C and Q. Our analyses confirm C-MPB373, C-P39, Q-Z780, Q-M848, and Q-Y4276 as the main founding haplogroups and identify traces of unsuccessful (pre-Q-F1096) or extinct (C-L1373*, Q-YP4010*) Y-chromosome lineages, indicating that haplogroup diversity of the founder populations that first entered the Americas was greater than that observed in the Indigenous component of modern populations. In addition, through a diachronic and phylogeographic dissection of newly identified Q-M848 branches, we provide the first Y-chromosome insights into the early peopling of the South American hinterland (Q-BY104773 and Q-BY15730) and on overlying inland migrations (Q-BY139813).