Neural stem cell transplantation in patients with progressive multiple sclerosis: an open-label, phase 1 study

Innovative pro-regenerative treatment strategies for progressive multiple sclerosis (PMS), combining neuroprotection and immunomodulation, represent an unmet need. Neural precursor cells (NPCs) transplanted in animal models of multiple sclerosis have shown preclinical efficacy by promoting neuroprotection and remyelination by releasing molecules sustaining trophic support and neural plasticity. Here we present the results of STEMS, a prospective, therapeutic exploratory, non-randomized, open-label, single-dose-finding phase 1 clinical trial (NCT03269071, EudraCT 2016-002020-86), performed at San Raffaele Hospital in Milan, Italy, evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal NPCs (hfNPCs) in 12 patients with PMS (with evidence of disease progression, Expanded Disability Status Scale >= 6.5, age 18-55 years, disease duration 2-20 years, without any alternative approved therapy). The safety primary outcome was reached, with no severe adverse reactions related to hfNPCs at 2-year follow-up, clearly demonstrating that hfNPC therapy in PMS is feasible, safe and tolerable. Exploratory secondary analyses showed a lower rate of brain atrophy in patients receiving the highest dosage of hfNPCs and increased cerebrospinal fluid levels of anti-inflammatory and neuroprotective molecules. Although preliminary, these results support the rationale and value of future clinical studies with the highest dose of hfNPCs in a larger cohort of patients

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Safety of humanized monoclonal antibodies against IL-5 in asthma: focus on reslizumab

Introduction: Reslizumab, a humanized mAb against IL-5, reduces the number of eosinophils in the blood and lungs. Based on efficacy and safety data from pivotal RCTs, reslizumab had been approved for use as an add-on maintenance treatment of severe asthma with an eosinophilic phenotype in adults who have a history of exacerbations despite receiving their current asthma medicines.Areas covered: Current literature on reslizumab has been reviewed with a specific focus on its safety profile in the treatment of severe asthma.Expert opinion: Large pivotal and supportive trials reinforce the view that reslizumab is well tolerated, with an acceptable safety profile in patients exposed for longer than 2 years. However, no or few data concerning safety in special populations such as smokers, those with immune- and cellular senescence, patients with comorbidities and those receiving multi-drug treatments are available as yet. Furthermore, we need to fully elucidate some fundamental issues such as the risk of anaphylaxis and the long-term risk-benefit ratio of the impact of depletion of eosinophils and the potential risk of malignancies induced by a treatment with this anti-IL-5 agent

Step-over fault zones controlling geothermal fluid-flow and travertine formation (Denizli Basin, Turkey)

In the Honalilar area (Denizli Basin, Turkey), the occurrence of banded Ca-carbonate veins and travertine de- posits, represented by a dismantled fissure ridge-type depositional system, are the evidence of a middle-late Pleistocene exhumed, shallow, hydrothermal system. Their occurrence offers the best opportunity to: (i) re- construct the fluid paths from the underground to the palaeo-surface, and (ii) analyse the role of fault zones in controlling the permeability and fluids circulation. Permeability developed in overstepping regional scale normal faults, with a slight left-lateral oblique-slip component. At the surface, faults favored the localization and development of a fissure ridge-type travertine deposit. At depth, the root of the hydrothermal system consists of W-E oriented fractures filled of up to 6.5 m thick Ca-carbonate veins, developed in a high dilatation zone. It corresponds to the step-over determined by the oblique-slip kinematics of the NW-striking main faults. The high dilatation step-over zone contrasted the progressive sealing induced by the concomitant Ca-carbonate deposition within the fractures, thus favoring permeability maintenance and fluids circulation for at least 200 ka. This evidence adds key inputs for predicting permeable volumes during geothermal exploration in areas affected by extensional tectonics. The main NW-oriented faults remained active even after the hydrothermal fluid flow, causing the dismantlement and progressive exhumation of the upper part of the hydrothermal system.In the Honalilar area (Denizli Basin, Turkey), the occurrence of banded Ca-carbonate veins and travertine deposits, represented by a dismantled fissure ridge-type depositional system, are the evidence of a middle-late Pleistocene exhumed, shallow, hydrothermal system. Their occurrence offers the best opportunity to: (i) reconstruct the fluid paths from the underground to the palaeo-surface, and (ii) analyse the role of fault zones in controlling the permeability and fluids circulation. Permeability developed in overstepping regional scale normal faults, with a slight left-lateral oblique-slip component. At the surface, faults favored the localization and development of a fissure ridge-type travertine deposit. At depth, the root of the hydrothermal system consists of W-E oriented fractures filled of up to 6.5 m thick Ca-carbonate veins, developed in a high dilatation zone. It corresponds to the step-over determined by the oblique-slip kinematics of the NW-striking main faults. The high dilatation step-over zone contrasted the progressive sealing induced by the concomitant Ca-carbonate deposition within the fractures, thus favoring permeability maintenance and fluids circulation for at least 200 ka. This evidence adds key inputs for predicting permeable volumes during geothermal exploration in areas affected by extensional tectonics. The main NW-oriented faults remained active even after the hydrothermal fluid flow, causing the dismantlement and progressive exhumation of the upper part of the hydrothermal system

Fractures, fluid flow and inherited structures in geothermal systems: inputs from the Fe-ore deposits of eastern Elba Island (Northern Apennines, Italy)

Geothermal systems in terrains affected by polyphase deformation have reservoirs with a 3D geometry that is always difficult to predict. In this paper we describe a fossil exhumed geothermal system exposed in eastern Elba Island that developed in a polyphase folded and faulted setting, which can help us to understand how geothermal fluids circulate in geological bodies with inherited structures. Geothermal circulation at Elba allowed the deposition of Fe-ore deposits (haematite/magnetite and pyrite) and altered rock volumes, which represent tracers of the palaeo-fluid flow. Normal and oblique-slip faults dissected a polyphase folded metasiliciclastic succession and produced a secondary permeability in the range of 5 × 10−13 to 5 × 10−16 m2. From the permeable fault zones acting as feeder conduits, geothermal fluids permeated the hydraulically connected metasiliciclastic rock bodies previously deformed by two generations of folds. Geothermal fluids followed the already defined geometry, thus giving rise to apparent folded mineralized levels. Fluid migration into the metasiliciclastic rocks was possible due to their chemical aggression, which favoured the dissolution and reprecipitation of quartz, and Fe-oxide and sulphide deposition. Renewed fluids maintained their chemical properties (pH value and temperature, mostly). This conclusion provides inputs for reconstructing geothermal conceptual models and evaluating the geothermal potentiality of exploitable areas developing in similar geological settings

Earthquake-triggered soft-sediment deformation structures (seismites) in travertine deposits

Earthquakes-related soft-sediment deformations (seismites) are relevant structures to help reconstructing the palaeoseismicity in a region. Nevertheless, although seismites have been described for a large variety of palaeo-environments and stratigraphic settings, they are rare and, in some cases, ambiguous structures. In this paper, we document, for the first time, impressive seismites affecting a latest Quaternary travertine deposit located in southern Tuscany (Serre di Rapolano, Italy). These structures are extremely relevant, as seismites have been never described for this kind of terrestrial deposits. The seismites developed within a 2.5 m thick stratigraphic succession made of alternating terrigenous and carbonate sediments, embedded within the travertine deposits. Earthquake produced liquefaction and fluidization of some terrigenous levels and the injection of fluidized silty sediments (dykes and sills) into carbonate and terrigenous levels; slumped levels and associated decollement surfaces produced highly non-cylindrical folds, overall induced by the loss of brittle shear strength along the basin slopes. The occurrence of these soft-sediment deformations implies an important seismic event that took place in a time spam encompassed between 84 ± 8 and 48.92 ± 5.08 ka, in an area characterized by low seismicity and scarce knowledge of its seismotectonic setting. Their spectacular exposition and preservation in saw-cuts of an abandoned quarry (Cava Oliviera quarry) highlights their relevance and importance

Evaluation of Cardiovascular Activity and Emotional Experience in Healthcare Workers (HCWs) Operating in COVID-19 Wards

The new 2019 coronavirus or SARS-CoV-2 has been the first biological agent to generate, in this millennium, such a global health emergency as to determine the adoption of public health measures. During this sanitary emergency, the emotional experience of healthcare workers (HCWs) has been hugely tested by several factors. In fact, HCWs have been exposed to greatly tiring physical, psychological and social conditions. The authors investigated the cardiocirculatory activity of a group of HCWs as well as how they perceived stress while working in COVID-19 wards. In particular, every HCW underwent a medical check, an electrocardiographic base exam, systolic and diastolic pressure measurement, and cardio frequency measurement. Furthermore, each HCW was provided with a cardiac Holter device (HoC) and a pressure Holter (Hop). Some psychological factors were considered in order to quantify the stress perceived by each HCW while at work through the administration of two questionnaires: the “Social Stigma towards Patients due to COVID Scale (SSPCS)” and the “Professional Quality of Life Scale (ProQOL)”. The HoC and HoP analysis results for HCWs working in COVID-19 OU wards showed significant variations in cardiocirculatory activity. From the analysis of the SSPCS questionnaire answers, it is clear that all of them showed a sense of duty towards their patients. The analysis of the ProQOL questionnaire answers showed that the prevailing attitude is fear; however, HCWs did not absolutely discriminate against those who had COVID-19 nor did they refuse to help those in need. Continuous monitoring of these employees, also carried out through occupational medicine surveillance, allows for the detection of critical conditions and the implementation of actions aimed at preventing chronic processes

Safety of humanized monoclonal antibodies against IL-5 in asthma: focus on reslizumab

Reslizumab, a humanized mAb against IL-5, reduces the number of eosinophils in the blood and lungs. Based on efficacy and safety data from pivotal RCTs, reslizumab had been approved for use as an add-on maintenance treatment of severe asthma with an eosinophilic phenotype in adults who have a history of exacerbations despite receiving their current asthma medicines. Areas covered: Current literature on reslizumab has been reviewed with a specific focus on its safety profile in the treatment of severe asthma. Expert opinion: Large pivotal and supportive trials reinforce the view that reslizumab is well tolerated, with an acceptable safety profile in patients exposed for longer than 2 years. However, no or few data concerning safety in special populations such as smokers, those with immune- and cellular senescence, patients with comorbidities and those receiving multi-drug treatments are available as yet. Furthermore, we need to fully elucidate some fundamental issues such as the risk of anaphylaxis and the long-term risk-benefit ratio of the impact of depletion of eosinophils and the potential risk of malignancies induced by a treatment with this anti-IL-5 agent

Evaluation of Cardiovascular Activity and Emotional Experience in Healthcare Workers (HCWs) Operating in COVID-19 Wards

The new 2019 coronavirus or SARS-CoV-2 has been the first biological agent to generate, in this millennium, such a global health emergency as to determine the adoption of public health measures. During this sanitary emergency, the emotional experience of healthcare workers (HCWs) has been hugely tested by several factors. In fact, HCWs have been exposed to greatly tiring physical, psychological and social conditions. The authors investigated the cardiocirculatory activity of a group of HCWs as well as how they perceived stress while working in COVID-19 wards. In particular, every HCW underwent a medical check, an electrocardiographic base exam, systolic and diastolic pressure measurement, and cardio frequency measurement. Furthermore, each HCW was provided with a cardiac Holter device (HoC) and a pressure Holter (Hop). Some psychological factors were considered in order to quantify the stress perceived by each HCW while at work through the administration of two questionnaires: the “Social Stigma towards Patients due to COVID Scale (SSPCS)” and the “Professional Quality of Life Scale (ProQOL)”. The HoC and HoP analysis results for HCWs working in COVID-19 OU wards showed significant variations in cardiocirculatory activity. From the analysis of the SSPCS questionnaire answers, it is clear that all of them showed a sense of duty towards their patients. The analysis of the ProQOL questionnaire answers showed that the prevailing attitude is fear; however, HCWs did not absolutely discriminate against those who had COVID-19 nor did they refuse to help those in need. Continuous monitoring of these employees, also carried out through occupational medicine surveillance, allows for the detection of critical conditions and the implementation of actions aimed at preventing chronic processes