VALUTAZIONE DELLE POTENZIALITÀ DEL BIOCHAR COME COMPONENTE DEI SUBSTRATI DI COLTIVAZIONE

The possibility of using biochar as a soil amendment for agricultural land has been intensively investigated, but it is only recently that biochar is proposed for greenhouse applications. Biochar can be used as a partial substitute of commercial peat for the cultivation of potting plants, so reducing the use of a non-renewable material like peat. In fact peat has a slow regrowth rate of 0.5-2 mm per year, and costs of extraction and transportation of peat are increasing. In this dissertation, the effects of four biochars added to a peat-based growing media are explored. Biochars are produced via pyro-gasification of plant derived feedstocks, (chipped and pelletized poplar and spruce wood), and analized for their properties useful to predict their behaviour in a potting mix. All the studied biochars are alkaline, show good physical stability (lack of shrinking), are richness in basic cations, particularly potassium, and show different particle size distributions. The first experiments carried on on mixtures of biochar and peat focuse on: 1) the liming power of biochars; 2) the influence of biochars on the pore water composition; 3) the effects of biochar application on the plant growth and nutrient uptake. When added to an acidic peat in a dose of 30% v/v , biochars neutralize both peat acidity and the acidification induced by root activity, that is inversely related to the size of particles and not influenced by biochars pH. Incubations of mixtures with and without plants highlight a dramatic influence of biochars on pore water composition.The poplar wood biochar induces an almost complete depletion of the fertilizer-derived NH4 +-N and high levels of NO3 --N in pore water, even though a decline over time is detected. On the contrary, in the sprucewood biochar added mixture NH4 +-N is immobilized in a lesser extent and only trace amounts of NO3 --N are detected. Further, the abilities of biochars to adsorb ammonia and nitrate are explored and a greater capacity for ammonia adsorption is detected. Then biochars are loaded with ammonium and an incubation test and a plant growth trial are performed on the ammonium-enriched materials added to a peat based growing media, compared with (NH4)2SO4 and with a loaded zeolite. Ammonia from the loaded biochars are more bioavailable than that carried by zeolite and both the studied biochars promote plant nitrogen uptake. Lastly, a trial is conducted in a commercial greenhouse using two biochars for total replacements of lime and partial substitution of the inorganic component (perlite). The growth of Ciclamen persicum plants results only slightly influenced by the biochars while pore water solution composition is deeply modified by the biochars. It can be concluded that biochar efficiently substitutes lime in buffering peat acidity and may be used as a partial replacement for peat and a source of potassium. Its highly reactive surfaces account its potential to significantly alter soil solution chemistry

Calcitonin gene-related peptide antagonists in pregnancy: a disproportionality analysis in VigiBase®

Background Current evidence on the safety of calcitonin gene–related peptide antagonists (CGRP-A) in pregnancy for the treatment of both episodic and chronic migraine is scarce and does not yet provide definitive information. By querying VigiBase$^{®}$, the World Health Organization global pharmacovigilance database, this study aimed to detect differences in the reporting frequency between CGRP-A and triptans in relation to pregnancy. Methods Disproportionality analyses on de-duplicated safety reports collected in VigiBase$^{®}$ as of 31.05.2023 reporting exposure to CGRP-A in pregnancy with or without pregnancy outcomes. A Reporting Odds Ratio (ROR) with a 95% confidence interval (CI) was used as a measure of disproportionality and the threshold for the detection of a signal of disproportionate reporting was set with a 95% CI lower limit > 1. Findings Four hundred sixty-seven safety reports reported exposure to CGRP-A in pregnancy, mostly originating from the United States of America (360/467, 77%), more frequently reported by patients (225/467, 48%), who were mainly females (431/467, 92%), and more frequently reported exposure to CGRP-A during pregnancy (400/467, 86%). Compared to triptans, no signals of disproportionate reporting were detected with CGRP-A either for the overall reporting of pregnancy-related safety reports (ROR 0.91, 95% CI 0.78–1.06), for the reporting of pregnancy outcomes (maternal and/or foetal/neonatal, ROR 0.54, 95% CI 0.45–0.66), or for the reporting of foetal/neonatal outcomes (ROR 0.53, 95% CI 0.41–0.68). Conclusions This study showed that, to date, there are no signals of increased reporting with CGRP-A compared to triptans in relation to pregnancy in VigiBase$^{®}$. Future pharmacovigilance studies are needed to confirm these findings

Safety profile of monoclonal antibodies targeting the calcitonin gene-related peptide system in pregnancy: Updated analysis in VigiBase®

Background: Safety data on the use of migraine preventive monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) system in pregnancy are limited. Methods: Updated pharmacovigilance assessment of the safety reports related to pregnancy associated with erenumab, galcanezumab, fremanezumab and eptinezumab, retrieved from VigiBase® as of 31 December 2021. As primary outcome, the whole group of monoclonal antibodies targeting the CGRP system was considered and sex and age subgroup disproportionality analyses using the reporting odds ratio (ROR) were conducted. Results: 286 safety reports were found: 116 (40.6%) on erenumab, 125 (43.7%) on galcanezumab, 39 (13.6%) on fremanezumab, 6 (2.1%) on eptinezumab. One hundred and forty-nine (52.1%) safety reports reported only drug exposure in relation to pregnancy while 137 (47.9%) also included ≥1 pregnancy outcomes: maternal outcomes (n = 64), spontaneous abortion (n = 63), foetal growth restriction (n = 1), prematurity (n = 8), neonatal outcomes (n = 13), and poor breastfeeding (n = 1). No specific patterns of maternal, foetal and neonatal toxicity were observed. Spontaneous abortion was not disproportionally more frequently reported with erenumab, galcanezumab, fremanezumab and eptinezumab compared with the entire database (ROR 1.1, 95% confidence interval, CI, 0.8–1.5), the entire database since 2018 (ROR 1.3, 95% CI 1.0–1.8), and triptans (ROR 1.2, 95% CI 0.8–1.9). Conclusions: This updated safety analysis on erenumab, galcanezumab, fremanezumab and eptinezumab in pregnancy showed no signals of foeto-maternal toxicity according to VigiBase® safety reports

Immune Checkpoint Inhibitors and Pregnancy: Analysis of the VigiBase® Spontaneous Reporting System

: In pregnancy, immune checkpoint pathways are involved in the maintenance of fetomaternal immune tolerance. Preclinical studies have shown that immune checkpoint inhibitors (ICIs) increase the risk of fetal death. Despite the fact that using ICIs in pregnant women and women of childbearing potential is not recommended, some case reports of ICI exposure in pregnancy have been published showing favorable fetal outcomes. This study aimed to gain further insight into ICI safety in pregnancy by querying VigiBase®, the World Health Organization's spontaneous reporting system. We performed raw and subgroup disproportionality analyses using the reporting odds ratio and comparing ICIs with the entire database, other antineoplastic agents, and other antineoplastic agents gathered in VigiBase® since 2011. Across 103 safety reports referring to ICI exposure during the peri-pregnancy period, 56 reported pregnancy-related outcomes, of which 46 were without concomitant drugs as potential confounding factors. No signals of disproportionate reporting were found for spontaneous abortion, fetal growth restriction, and prematurity. In light of the expanding indications of ICIs, continuous surveillance by clinicians and pharmacovigilance experts is warranted, along with pharmacoepidemiological studies on other sources of real-world evidence, such as birth records, to precisely assess ICI exposure during the peri-pregnancy period and further characterize relevant outcomes

Immune Checkpoint Inhibitors and Pregnancy: Analysis of the VigiBase® Spontaneous Reporting System

In pregnancy, immune checkpoint pathways are involved in the maintenance of fetomaternal immune tolerance. Preclinical studies have shown that immune checkpoint inhibitors (ICIs) increase the risk of fetal death. Despite the fact that using ICIs in pregnant women and women of childbearing potential is not recommended, some case reports of ICI exposure in pregnancy have been published showing favorable fetal outcomes. This study aimed to gain further insight into ICI safety in pregnancy by querying VigiBase®, the World Health Organization’s spontaneous reporting system. We performed raw and subgroup disproportionality analyses using the reporting odds ratio and comparing ICIs with the entire database, other antineoplastic agents, and other antineoplastic agents gathered in VigiBase® since 2011. Across 103 safety reports referring to ICI exposure during the peri-pregnancy period, 56 reported pregnancy-related outcomes, of which 46 were without concomitant drugs as potential confounding factors. No signals of disproportionate reporting were found for spontaneous abortion, fetal growth restriction, and prematurity. In light of the expanding indications of ICIs, continuous surveillance by clinicians and pharmacovigilance experts is warranted, along with pharmacoepidemiological studies on other sources of real-world evidence, such as birth records, to precisely assess ICI exposure during the peri-pregnancy period and further characterize relevant outcomes

Four cases of audio-vestibular disorders related to immunisation with SARS-CoV-2 mRNA vaccines.

To gain medical insight into the clinical course and safety of otolaryngologic disorders following immunisation with severe acute respiratory coronavirus (SARS-CoV-2) mRNA-based vaccines. Case description. We report four cases of transient audio-vestibular symptoms, which occurred shortly after inoculation of two BNT162b2 (Pfizer-BioNTech <sup>®</sup> ) and mRNA-1273 (Moderna®) vaccines. Hearing loss was unilateral in all cases and recovered at least partially: it was associated with persistent gait instability in two cases, after 1 and 7 months. Trigger mechanisms underpinning audio-vestibular impairment remain uncertain. Immune tolerance mechanisms with off-target innate activation of T-lymphocytes may be involved in vestibulocochlear nerve disorders, as for other cranial nerves involvement. The occurrence of audio-vestibular manifestations following mRNA-based vaccines needs ENT monitoring to support their causality in such rare vaccine-related adverse events. Audio-vestibular disorders appeared of transitory nature, including hearing loss, and should not deter further efforts in large-scale vaccination campaigns against SARS-CoV-2

Lymphatic clearance of the brain: perivascular, paravascular and significance for neurodegenerative diseases

The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (A?). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer’s disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that A? is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of A? in the glia limitans in Alzheimer’s disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of A?. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance

The Dark Purple Side of Ceftriaxone: A Case Report on Leucocytoclastic Vasculitis

We present a case of an 85-year-old woman diagnosed with uncomplicated pyelonephritis, who was treated with intravenous ceftriaxone. Her chronic medications were phenprocoumon, diltiazem and bisoprolol. During the infectious phase, the patient presented tachycardia – despite high-dose beta-blocker treatment – and developed left acute heart failure, with acute renal failure (pre-renal origin). After introduction of furosemide diuretic therapy, clinical conditions improved and better control of the volemic status and heart rate was achieved. Several days after ceftriaxone and digoxin therapy initiation, worsening multiple non-blanching palpable purpuric lesions with bullae and papules, limited to the lower extremities, were noted. Skin biopsy was performed and a diagnosis of leucocytoclastic vasculitis, with associated panniculitis, was made. Ceftriaxone was discontinued and systemic corticosteroids were introduced, with a clear improvement in the cutaneous condition