SARS-CoV-2-Related Olfactory Dysfunction: Autopsy Findings, Histopathology, and Evaluation of Viral RNA and ACE2 Expression in Olfactory Bulbs.

BACKGROUND: The COVID-19 pandemic has been a health emergency with a significant impact on the world due to its high infectiousness. The disease, primarily identified in the lower respiratory tract, develops with numerous clinical symptoms affecting multiple organs and displays a clinical finding of anosmia. Several authors have investigated the pathogenetic mechanisms of the olfactory disturbances caused by SARS-CoV-2 infection, proposing different hypotheses and showing contradictory results. Since uncertainties remain about possible virus neurotropism and direct damage to the olfactory bulb, we investigated the expression of SARS-CoV-2 as well as ACE2 receptor transcripts in autoptic lung and olfactory bulb tissues, with respect to the histopathological features. METHODS: Twenty-five COVID-19 olfactory bulbs and lung tissues were randomly collected from 200 initial autopsies performed during the COVID-19 pandemic. Routine diagnosis was based on clinical and radiological findings and were confirmed with post-mortem swabs. Real-time RT-PCR for SARS-CoV-2 and ACE2 receptor RNA was carried out on autoptic FFPE lung and olfactory bulb tissues. Histological staining was performed on tissue specimens and compared with the molecular data. RESULTS: While real-time RT-PCR for SARS-CoV-2 was positive in 23 out of 25 lung samples, the viral RNA expression was absent in olfactory bulbs. ACE2-receptor RNA was present in all tissues examined, being highly expressed in lung samples than olfactory bulbs. CONCLUSIONS: Our finding suggests that COVID-19 anosmia is not only due to neurotropism and the direct action of SARS-CoV-2 entering the olfactory bulb. The mechanism of SARS-CoV-2 neuropathogenesis in the olfactory bulb requires a better elucidation and further research studies to mitigate the olfactory bulb damage associated with virus action.

Risk of Repeated Adverse Effects following Booster Dose of mRNA COVID-19 Vaccine: Results from the MOSAICO Study.

The successful deployment of safe and effective vaccines against coronavirus disease 2019 (COVID-19) has been crucial in reducing the global disease burden. Owing to the need for vaccination series over time, continuous observational studies are needed to estimate the COVID-19 vaccine response in real-world conditions. In particular, the detection, assessment, and understanding of adverse effects following immunization (AEFI) with a COVID-19 vaccine are crucial to better address vaccination strategies. Therefore, this study aimed to investigate the risk of repeated AEFI post-administration of a booster dose of mRNA COVID-19 vaccine in a sample of healthcare workers (HCWs) in an Italian teaching hospital. The data on any local and systemic AEFI were studied in multivariate Poisson regression analyses to model the association between the incidence of each postvaccination symptom and its prior reporting after the administration of the previous doses. Overall, compared with the primary vaccination series, the majority of post-third dose AEFI were less reported. The results from multivariable models showed that the likelihood of reporting an AEFI after the third dose was higher in those who experienced the same postvaccination symptom after the second dose (all AEFI except for itch at injection site) and, although not significant for all AEFI, after the first dose. Any associations with age, gender, smoking habits, previous SARS-CoV-2 infection and other characteristics, as well as the health impact of AEFI were also assessed. Taken together, the results from this research support reframe AEFI symptoms as signals of a robust postvaccination reaction as well as of common vaccine response, and they add important data to inform booster vaccination strategies in HCWs and, extensively, in the adult population.

Time-Varying Effect of Hybrid Immunity on the Risk of Breakthrough Infection after Booster Dose of mRNA COVID-19 Vaccine: The MOSAICO Study.

This longitudinal observational study investigated the risk of breakthrough SARS-CoV-2 infection up to 6 months after a booster dose of an mRNA COVID-19 vaccine in infection-naïve vs. previously infected healthcare workers (HCWs), and whether this difference varied over time. A Cox proportional hazard regression model with Aalen's additive analysis was fitted to examine the association between the risk of infections and predictor variables. Overall, we observed an incidence rate of 2.5 cases per 1000 person-days (95% confidence interval [CI] 2.0-3.0), which dropped at 0.8 per 1000 person-days (95% CI 0.3-2.0) in recipients with prior SARS-CoV-2 infection. The fitted analysis indicated an adjusted hazard ratio of 0.32 (95% CI 0.13-0.80; p-value = 0.01) for those with hybrid immunity with a slope that became steeply negative roughly starting from day 90. No difference was seen according to participants' smoking habits. Characteristics of infected HCWs were also described. Our study quantifies the time-varying effects of vaccine-induced and hybrid immunity after the booster dose (during the Omicron variant predominance in Italy) and observed that the protection waned more rapidly in infection-naïve recipients starting from the third month. The results add important evidence that can be used to inform COVID-19 vaccination strategies.

Comment on Kopanska et al. Disorders of the Cholinergic System in COVID-19 Era-A Review of the Latest Research. Int. J. Mol. Sci. 2022, 23, 672.

We read the recent review article by Marta Kopanska et al. [...].

SARS-CoV-2 infection after vaccination in Italian health care workers: a case report.

Following the approval of COVID-19 vaccination program by EMA and national authorities, an immunization campaign started in Italy with BNT162b2mRNA vaccine, initially focused on healthcare workers. The active immunization was monitored by systemic antibody titration and continuous surveillance was guaranteed by antigenic/molecular tests on swabs. Cases of infection have been recently observed in vaccinated healthcare workers. Herein we describe an outbreak of infection occurring in five physicians out of 656 healthcare workers belonging to a private hospital, referring mild symptoms of COVID-19. Healthcare workers underwent complete vaccination and screening for antibody titration. Five out of 656 healthcare workers were tested positive for SARS-CoV-2 in nasopharyngeal swabs and referred mild COVID-19 symptoms. Molecular analyses were carried out to identify possible variants of Spike protein. Their genotyping performed on RNA extracts highlighted the presence of del69/70, N501Y, A570D, and 1841A > G (D614G) sequence variants, all indicative of VOC 202012/01-lineage B.1.1.7, suggesting a common source of infection. These cases might represent a serious emergency because outbreaks can compromise frail patients with important concomitant diseases.

Response to BNT162b2 mRNA COVID-19 vaccine among healthcare workers in Italy: a 3-month follow-up.

This study investigated the response to BNT162b2 mRNA COVID-19 vaccine among healthcare workers (HCWs) in an Italian teaching hospital. 444 participants were surveyed with either multiple RT-PCR assays for detection of SARS-CoV-2 nucleic acid in nasopharyngeal swabs or serology testing for the research of virus-specific immunoglobulins. Adverse events following immunization (AEFI) were reported. Two weeks after the first dose anti-SARS-CoV-2 antibodies exceeded reactivity cut-off in 82.5% the participants. Four HCWs tested positive at nasopharyngeal swab after 3 months. More than three-quarters reported AEFIs. Our findings offer an insight regarding the vaccine response after 3 months from its administration, with a special focus on effectiveness data, as well as the type and number of AEFIs complained by HCW recipients. The presented study may serve as reference for future research which will be necessary to explore the long-term safety of this vaccine, especially in population at high risk for infection, such as HCWs.

Overview of Facebook Use by Hospitals in Italy: A Nationwide Survey during the COVID-19 Emergency.

Background: Facebook is the most popular social network across the world and also allows users access to health information. Our study presents an overview of the official Facebook profiles of hospitals in Italy (n = 1351) and how much they are used. Methods: All hospitals were surveyed on the number of Facebook posts in May (post-lockdown) and October (second pandemic wave) 2020. The number of followers, the creation date of the official page, and the frequency of publication-that is, the average number of days between two subsequent posts-were determined. Results: In Italy, only 28% (n = 379) of the hospitals had official Facebook pages, of which 20.6% (n = 78) were public hospitals, and 79.4% (n = 301) were private hospitals. Of the hospitals with Facebook pages, 49.1% used them every week, and public hospitals published more often. Conclusions: Despite the differences between regions and types of management, the number of hospitals in Italy that use Facebook as a tool for the public dissemination of health information is still low. Hospitals should adopt an effective communication strategy using social networks to improve the quality of health care.

Could Small Neurotoxins-Peptides be Expressed during SARS-CoV-2 Infection?

SARS-CoV-2 pathogenesis has been recently extended to human central nervous system (CNS), in addition to nasopharyngeal truck, eye, lung and gut. The recent literature highlights that some SARS-CoV-2 spike glycoprotein regions homologous to neurotoxin-like peptides might bind to human nicotinic Acetyl-Choline Receptors (nAChRs). Spike-nAChR interaction can probably cause dysregulation of CNS and cholinergic anti-inflammatory pathways and uncontrolled immune-response, both associated to a severe COVID-19 pathophysiology. Herein, we hypothesize that inside the Open Reading Frame (ORF) region of spike glycoprotein, the RNA polymerase can translate small neurotoxic peptides by means of a "jumping mechanism" already demonstrated in other coronaviruses. These small peptides can bind the snAChRs instead of Spike glycoproteins. A striking homology occurred between these small peptides observed by sequence retrieval and proteins alignment. Acting as nAChRs antagonists, these small peptides (conotoxins) could be the explanation for the extrapulmonary clinical manifestations (neurological, hemorrhagic and thrombotic expressions, the prolonged apnea, the cardiocirculatory collapse, the heart arrhythmias, the ventricular tachycardia, the body temperature alteration, the electrolyte K+ imbalance and finally the significant reduction of butyryl cholinesterase (BuChE) plasma levels, as observed in COVID-19 patients. Several factors might induce the expression of these small peptides, including microbiota. The main hypothesis regarding the presence of these small peptides opens a new scenario on the etiology of COVID-19 clinical symptoms observed so far, including the neurological manifestations.

Adverse drug reactions during hepatitis C treatment with direct-acting antivirals: The role of medication errors, their impact on treatment discontinuation and their preventability. New insights from the Campania Region (Italy) spontaneous reporting system.

WHAT IS KNOWN AND OBJECTIVE: Medication errors, such as unnecessary treatment discontinuation during treatment with direct-acting antivirals (DAAs), can lead to imbalances in the benefit-to-risk ratio. This risk is especially high when the medication error leads to adverse drug reactions (ADRs). However, to date, evidence on the frequency of this phenomenon is scarce. This study aims to provide better insight into ADRs possibly due to medication errors leading to DAA discontinuation and their preventability. METHODS: The Italian Pharmacovigilance Network database was used to extract individual case safety reports (ICSRs) generated from July 2012 to March 2017 via the Campania Region (Italy) spontaneous reporting system. ICSRs that included ledipasvir/sofosbuvir, ombitasvir/paritaprevir/ritonavir, dasabuvir, daclatasvir, sofosbuvir, simeprevir or elbasvir/grazoprevir as suspected drugs were included in this study. A preventability assessment was then performed utilizing the "P-Method," an algorithm that evaluates known risk factors due to medication errors that can be detected in ICSRs. RESULTS AND DISCUSSION: Of the 355 cases included in this study, 6 (1.69%) were classified as preventable and 52 (14.6%) were classified as potentially preventable. The most frequently identified critical criteria (risk factor) for preventable or potentially preventable cases were drug-drug interactions and incorrect drug dosing as part of the antiviral treatment scheme. In total, 89 of the 355 cases (25.1%) discontinued use of the DAAs due to ADRs, of which 20 of the 89 cases (22.5%) were due to an unimportant medical event as classified by the European Medicine Agency important medical event list. WHAT IS NEW AND CONCLUSION: This study found a proportion of preventable/potentially preventable ADRs involving DAA, which could be improved in the Campania Region (Italy). Additionally, the study identified a high proportion of seemingly unnecessary DAA discontinuations among patients who experienced ADRs.

[Day surgery: the role and training needs of nurses]. / La Formazione dell'Infermiere in Day Surgery.

Medicine and health care are increasingly directed towards the achievement of high quality standards and of costs reduction. It is in this framework that same-day surgery finds its role, being able to satisfy both of the above needs. Despite its recognized benefits, in Italy this efficient model of hospitalization still meets several obstacles and the ratio of services provided in day hospital with respect to ordinary hospital admission is about 1 to 3. Day Surgery services depend on team work and the nurse's role is of utmost importance and responsibility since it involves both clinical care and managerial activities. Through a careful analysis of the skills required of a day surgery nurse, the authors discuss aspects of nurses' training in view of the pre- and post-graduate courses currently offered, including on-the-job training.

Current management of hepatocellular cancer.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, being the fifth most frequent cancer worldwide. It usually occurs in the setting of chronic liver disease and has a poor prognosis if untreated. Following the diagnosis, this disease requires multidisciplinary management. Orthotopic liver transplantation is theoretically the best treatment for early, unresectable HCC. However, the major practical obstacle is the extreme shortage of organs, which makes this a practical option only in selected patients. In this report we describe new advancements in diagnosis, classification, and treatment that have emerged in the field of HCC in recent years.

Current role of hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis from colorectal cancer.

Peritoneal carcinomatosis is one of the most common routes of dissemination of colorectal cancer (CRC). It is encountered in 7% of patients at primary surgery, while it develops in about 4% to 19% of patients after curative surgery and in up to 44% of patients with recurrent CRC. Peritoneal involvement from colorectal malignancies has been considered traditionally as a manifestation of terminal disease, due to limited response to conventional surgical and chemotherapeutic treatments. In the past few years the introduction of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion has shown promising results in selected patients. Currently, the surgical management of peritoneal surface malignancies of colonic origin with this combined locoregional therapy has resulted in a significant improvement in survival of these patients. However, further controlled studies will help to standardize indications and the technique of this locoregional therapy in order to achieve an improvement of morbidity and mortality rates.

Current management strategy of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) still remains a considerable challenge for surgeons. Surgery, including liver transplantation, is the most important therapeutic approach for patients with this disease. HCC is frequently diagnosed at advanced stages and has a poor prognosis with a high mortality rate even when surgical resection has been considered potentially curative. This brief report summarizes the current status of the management of this malignancy and includes a short description of new pharmacological approaches in HCC treatment.

[The Poland' syndrome. Case report]. / La sindrome di Poland. Caso clinico.

A case of Poland's syndrome in a 2-year-old female is described. The patient had come to our Emergency department for abdominal pain. The thorax's asymmetric depression and the brachysyndactyly of the right hand are fundamental elements to make Poland's syndrome diagnosis in our patient. In this report, the different formes of Poland's syndrome, the classification and the indications for a surgical intervention are described. Besides the importance of a precocious diagnosis is underlined, due to avoid complications related to late rehabilitation and multidisciplinary approach to the patient.