Role of imaging and adrenal venous sampling techniques in the diagnosis of primary aldosteronism

Background: Primary aldosteronism (PA) is a rare condition characterized by inappropriately high secretion of aldosterone, independently of the renin-angiotensin system, not suppressed by sodium loading test. PA represents the most common cause of secondary hypertension and its early detection and treatment can help reduce the cardiovascular (CV) risk. Case presentation: We report on a 42-year-old man who was referred to an outpatients’ clinic reporting headache and vomiting associated with hypertension and was discharged with oral antihypertensive medication (irbesartan) and low-sodium diet. Three years later, he underwent further hospitalization for muscle pain in lower limb associated with severe hypokalemia (1.7 mmol/L) and elevated creatine phosphokinase (CPK) levels (2634 U/L). Abdominal CT scan excluded the presence of adrenal lesions. Acute intravenous potassium chloride (KCL) supplementation normalized serum potassium level and the patient was discharged with diagnosis of rhabdomyolysis and hypokalemia and with antihypertensive medication (spironalactone: 100 mg/day and amlodipine: 5 mg/day) and oral KCL supplementation (600 mg/day). After pharmacological washout, an inappropriately high aldosterone concentration (75.10 pg/ml) and very low renin level (1.10 pg/ml) were detected. PA diagnosis was confirmed by oral saline infusion test (SIT). Aldosterone levels did not normalize after dexamethasone suppression testing. Abdominal MRI showed a nodule measuring 6 mm in the right adrenal. A subsequent adrenal venous sampling (AVS) confirmed the unilateral (right) lateralization of the aldosterone hypersecretion. Conclusion: Although invasive, AVS is the gold standard test to differentiate PA subtypes in patients who can be considered ideal candidates for unilateral adrenalectomy

Vaccination coverage in healthcare workers: a multicenter cross-sectional study in Italy

IntroductionIn recent years, a phenomenon known as "vaccine hesitancy" has spread throughout the world, even among health workers, determining a reduction in vaccination coverage (VC). A study aimed at evaluating VC among healthcare workers (HCWs) in 10 Italian cities (L'Aquila, Genoa, Milan, Palermo, Sassari, Catanzaro, Ferrara, Catania, Naples, Messina) was performed.Materials and methodsAnnex 3 of the Presidential Decree n. 445 of 28 December 2000 was used to collect information on the vaccination status of HCWs. The mean and standard deviation (SD) were calculated with regard to the quantitative variable (age), while absolute and relative frequencies were obtained for categorical data (sex, professional profile, working sector, vaccination status). The connection between VC and the categorical variables was evaluated by chi-square method (statistical significance at p<0.05). The statistical analyses were performed by SPSS and Stata software.ResultsA total of 3,454 HCWs participated in the project: 1,236 males and 2,218 females. The sample comprised: physicians (26.9%), trainee physicians (16.1%), nurses (17.2%) and other professional categories (9.8%). Low VC was generally recorded. Higher VC was found with regard to polio, hepatitis B, tetanus and diphtheria, while coverage was very low for measles, mumps, rubella, pertussis, chickenpox and influenza (20-30%). ConclusionsThis study revealed low VC rates among HCWs for all the vaccinations. Measures to increase VC are therefore necessary in order to prevent HCWs from becoming a source of transmission of infections with high morbidity and/or mortality both within hospitals and outside

Clinical and molecular description of the first Italian cohort of 33 subjects with hypophosphatasia

IntroductionHypophosphatasia (HPP) is a rare genetic disease caused by inactivating variants of the ALPL gene. Few data are available on the clinical presentation in Italy and/or on Italian HPP surveys.MethodsThere were 30 suspected HPP patients recruited from different Italian tertiary cares. Biological samples and related clinical, biochemical, and anamnestic data were collected and the ALPL gene sequenced. Search for large genomic deletions at the ALPL locus (1p36) was done. Phylogenetic conservation and modeling were applied to infer the effect of the variants on the protein structure.ResultsThere were 21 ALPL variants and one large genomic deletion found in 20 out of 30 patients. Unexpectedly, NGS-driven differential diagnosis allowed uncovering three hidden additional HPP cases, for a total of 33 HPP subjects. Eight out of 24 coding variants were novel and classified as “pathogenic”, “likely pathogenic”, and “variants of uncertain significance”. Bioinformatic analysis confirmed that all the variants strongly destabilize the homodimer structure. There were 10 cases with low ALP and high VitB6 that resulted negative to genetic testing, whereas two positive cases have an unexpected normal ALP value. No association was evident with other biochemical/clinical parameters.DiscussionWe present the survey of HPP Italian patients with the highest ALPL mutation rate so far reported and confirm the complexity of a prompt recognition of the syndrome, mostly for HPP in adults. Low ALP and high VitB6 values are mandatory for the genetic screening, this latter remaining the gold standard not only to confirm the clinical diagnosis but also to make differential diagnosis, to identify carriers, to avoid likely dangerous therapy in unrecognized cases

Reproducibility Package for 'Identifying risks in datasets for automated decision–making'

Our daily life is profoundly affected by the adoption of automated decision making (ADM) systems due to the ongoing tendency of humans to delegate machines to take decisions. The unleashed usage of ADM systems was facilitated by the availability of large-scale data, alongside with the deployment of devices and equipment. This trend resulted in an increasing influence of ADM systems' output over several aspects of our life, with possible discriminatory consequences towards certain individuals or groups. In this context, we focus on input data by investigating measurable characteristics which can lead to discriminating automated decisions. In particular, we identified two indexes of heterogeneity and diversity, and tested them on two datasets. A limitation we found is the index sensitivity to a large number of categories, but on the whole results show that the indexes reflect well imbalances in the input data. Future work is required to further assess the reliability of these indexes as indicators of discrimination risks in the context of ADM, in order to foster a more conscious and responsible use of ADM systems through an immediate investigation on input data

Low-Energy Extracorporeal Shock-Wave Therapy in the Treatment of Chronic Insertional Achilles Tendinopathy: A Case Series

Introduction. We report the results of a series of 40 patients with chronic insertional Achilles tendinopathy treated with low-energy ESWT after the failure of a 3-month program of eccentric exercises alone. Methods and Materials. 40 patients, 28 (70%) males and 12 (30%) females, were treated between January and December 2014. All patients were previously treated with only eccentric exercises for a 3-month period. The treatment protocol included 4 sessions of ESWT with a 2-week interval, from 800 shots in each one (4 Hz, 14 KeV), together with eccentric exercises. Visual Analogue Scale (VAS) and American Orthopedic Foot and Ankle Society (AOFAS) Hindfoot score were recorded. Results. At the 12-month follow-up, 26 (65.0%) patients did not complain about pain (VAS < 2), 11 (27.5%) patients got back to normal activities despite residual pain (VAS 2–4), and 3 (7.5%) of the patients still complained about pain (VAS > 4). There was no significative improvement in both scores after eccentric exercises alone. Mean VAS improvement was 5.8±1.3 SD points (P<0.001). Mean AOFAS Hindfoot score improvement was 19.8±5.0 SD points (P<0.001). Conclusions. ESWT is recommended, in combination with an eccentric exercise program, in patients with chronic Achilles tendinopathy being both insertional and not

Efficacy of Intravenous Hydrocortisone Treatment in Refractory Neonatal Seizures: A Report on Three Cases

Neonatal seizures are the most common neurological emergency, and neonatal status epilepticus (NSE) remains a controversial entity, with no general consensus about its definition and treatment. Here, we report on three newborns with NSE refractory to first- and second-line antiepileptic drugs successfully treated with intravenous (IV) hydrocortisone. The patients had previously failed therapy with levetiracetam, phenobarbital and midazolam, showing persistent clinical and electrical seizures. Modulation of brain inflammation triggered during prolonged epileptic activity has been thought to potentially explain the beneficial effects of anti-inflammatory treatment

Digital Twin Components for Geophysical Extreme Phenomena: the example of Volcanic Hazards within the DT-GEO project

The project Digital Twin for GEOphysical extremes-(DT-GEO) aims to use Digital Twin Components to create replicas of physical systems, serving as a virtual laboratory to study natural extreme events. The ratio- nale is the intrinsic risks of potentially catastrophic events to anthropic activities, infrastructures, and cultural heritage. In the framework of the project, this paper describes, how the DTC workflow architecture is designed, focusing on flexibility, scalability, and maintainability, and how it is further developed. To demonstrate how ICT efforts can expand horizons in Geosciences, an application to volcanic hazard is presented taking as a case study the 2019 volcanic eruption of Raikoke (Kuril Islands).We acknowledge the Project DT-GEO: Digital Twin for GEOphysical extremes - funded by Horizon Europe under the grant agreement No 101058129, https://cordis.europa.eu/project/id/10105812

Digital Twin Components in Volcanology

Interdisciplinary digital twins are becoming able to mimic the different Earth system domains with unrivalled precision, providing analyses, forecasts, uncertainty quantification, and ¿what if¿ scenarios for natural and anthropogenic hazards from their genesis to propagation and impacts. The EU DT-GEO project (2022-2025) is deploying a prototype digital twin on geophysical extremes consisting of interrelated Digital Twin Components (DTCs), intended as self-contained containerised entities embedding simulation codes, Artificial Intelligence (AI) layers, large volumes of nearly-real-time data streams, data assimilation methodologies, and overarching workflows for deployment and execution of single or coupled DTCs in centralised High Performance Computing (HPC) and virtual cloud computing Research Infrastructures (RIs). These DTCs, actually a first step towards a digital twin on Geophysical Extremes integrated in the Destination Earth (DestinE) initiative, will deal with geohazards from earthquakes, volcanoes, and tsunamis by harnessing world-class computational (EuroHPC) and data (EPOS) Research Infrastructures, operational monitoring networks, and leading-edge research and academia partnerships. In particular, 4 DTCs of the 12 in DT-GEO will address different volcanic hazards. DTC-V1 will merge multi-parametric data from ground- based and remote observation systems (on-site monitoring networks and satellites) with global modelling of magma and rock dynamics and with AI approach. DTC-V2 will merge real-time geostationary satellite observations with the FALL3D model using the on-line data assimilation PDAF system to generate deterministic and ensemble-based probabilistic forecast products. DTC-V3 will merge real-time multi- parametric data from ground-based and remote observation systems with deterministic modelling of lava flow propagation and inundation areas including Bayesian modelling of vent opening. Finally, DTC-V4 will consider air-quality data and AI in a gas dispersal forecast context to improve our operational Early Warning System

Peri-Personal Space Tracing by Hand-Blink Reflex Modulation in Patients with Chronic Disorders of Consciousness

: The assessment of awareness in patients with chronic Disorders of Consciousness (DoC), including Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), is challenging. The level of awareness impairment may depend on the degree of deterioration of the large-scale cortical-thalamo-cortical networks induced by brain injury. Electrophysiological approaches may shed light on awareness presence in patients with DoC by estimating cortical functions related to the cortical-thalamo-cortical networks including, for example, the cortico-subcortical processes generating motor responses to the perturbation of the peri-personal space (PPS). We measured the amplitude, latency, and duration of the hand-blink reflex (HBR) responses by recording electromyography (EMG) signals from both the orbicularis oculi muscles while electrically stimulating the median nerve at the wrist. Such a BR is thought to be mediated by a neural circuit at the brainstem level. Despite its defensive-response nature, HBR can be modulated by the distance between the stimulated hand and the face. This suggests a functional top-down control of HBR as reflected by HBR features changes (latency, amplitude, and magnitude). We therefore estimated HBR responses in a sample of patients with DoC (8 MCS and 12 UWS, compared to 15 healthy controls -HC) while performing a motor task targeting the PPS. This consisted of passive movements in which the hand of the subject was positioned at different distances from the participant's face. We aimed at demonstrating a residual top-down modulation of HBR properties, which could be useful to differentiate patients with DoC and, potentially, demonstrate awareness preservation. We found a decrease in latency, and an increase in duration and magnitude of HBR responses, which were all inversely related to the hand-to-face distance in HC and patients with MCS, but not in individuals with UWS. Our data suggest that only patients with MCS have preserved, residual, top-down modulation of the processes related to the PPS from higher-order cortical areas to sensory-motor integration network. Although the sample size was relatively small, being thus our data preliminary, HBR assessment seems a rapid, easy, and first-level tool to differentiate patients with MCS from those with UWS. We may also hypothesize that such a HBR modulation suggests awareness preservation