Enhancing Physicians' Autonomy through Practical Trainings.

Background: In medical emergencies adherence to standardized clinical protocols is crucial to ensure a better outcome for patients. Newly qualified physicians may play several roles in serving the National Health Service (substituting general practitioners, on-call duty, working in emergency rooms, etc.) in Italy. In these situations, the physician may have to manage critical patients autonomously. Moreover, newly qualified physicians may show a considerable deficiency in routine medical activities. In fact, many universities do not provide a practical simulation training programme, which is why a substantial number of students only face clinical emergencies when they start working after graduation. Study design: A cross-sectional study was performed by engaging medical doctors. Both experienced physicians and newly licensed physicians (graduated less than 24 months ago) were included in the study. Methods: A questionnaire was distributed to each participant during SIMED's Courses from June 2021 to December 2022. The questionnaire consisted of two sections. The first one analyzed participation in standardized practical courses on medical emer gencies (Basic Life Support, Advanced Cardiac Life Support, International Trauma Life Support and a course on Advanced Airway Management). The second section analyzed the perceived autonomy of health professionals in the management of five different work settings, using a 5-point likert scale. Results: 2,168 questionnaires were analyzed, of which 68.7% were from newly qualified doctors and 31.3% from more experienced doctors The highest rate of physicians who undertook training courses was achieved for the basic life support course (77.5%) and the lowest rate for the advanced trauma course (15.9%). Physicians perceive themselves the highest autonomy in Primary Care setting (63.1%), while in the Emergency Department they perceive themselves with less autonomy (24.0%). In the analyzed sample, experienced physicians show a higher percentage of autonomy than newly qualified doctors (31.4% vs 8.1%) in all scenarios. Conclusions: Our analysis shows a possible correlation between the self-perceived autonomy of physicians and attending practical simulation courses. Although the role of training through practical courses is relevant, the percentage of trained professionals is insufficient and therefore the implementation of practical training projects has to be encouraged.

Influenza and Covid-19 Vaccination in 2023: a descriptive analysis in two Italian Research and Teaching Hospitals. Is the On-Site strategy effective?

Introduction: Vaccinations represent an extremely effective tool for the prevention of certain infectious diseases - such as influenza and COVID-19 -, particularly for those categories at risk due to both their frail condition or professional exposure, such as healthcare workers. The aim of this study is to describe the course of the anti-influenza and anti-COVID-19 vaccination campaign at two Research Hospitals in Milan, Italy. Study design: Multicentre, cross-sectional study. Methods: For the 2023-24 vaccination campaign, the two facilities opted for two different approaches. At the Hospital A, two dif-ferent strategies for vaccinating healthcare workers were implemented: a fixed-site vaccination clinic and two mobile vaccination groups run by Public Health residents of the University of Milan. At the Hospital B, on the other hand, a single fixed-site outpatient clinic run by Public Health residents of the University of Milan was used. On the occasion of the campaign, a survey was also carried out using anonymous online questionnaires to investigate healthcare workers attitudes towards vaccination. Results: A total of 1,937 healthcare workers were vaccinated: 756 were immunized against influenza only, 99 against COVID-19 only, and 1,082 against both. The results show a substantial difference in vaccination adherence among medical and nursing staff compared to other professional categories. In particular, the category with the highest vaccination adhesion turned out to be that of medical doctors with 55.7% adhesion while, on the contrary, the category with the lowest adhesion turned out to be that of auxiliary personnel characterized by 7.4% adhesion. At the same time, the comparison between the two hospital facilities showed a double adherence rate by the staff of Hospital A as regards both the flu vaccine (40.6% and 20.1%) and the anti-COVID-19 vaccine (26.4% and 12.3%). Finally, the survey showed that the attitude towards influenza vaccination is lower among auxiliary staff in terms of both knowledge and vaccination attitude. Conclusions: The results of the study show a vaccination adherence in line with that of previous years, although lower than the values recommended by the principal national and international Organizations. The analysis of the differences between the two facilities and the surveys carried out will allow for the implementation of targeted interventions to increase adherence in future campaigns.

Association between Mediterranean diet and dementia and Alzheimer disease: a systematic review with meta-analysis.

BACKGROUND: Dementia affects 5-8% of the population aged over 65 years (~50 million worldwide). Several factors are associated with increased risk, including diet. The Mediterranean diet (MedDiet) has shown potential protective effects against several chronic diseases. AIMS: This systematic review with meta-analysis aim was to assess the association between adherence to the MedDiet and the risk of dementia in the elderly. METHODS: PRISMA-2020 guidelines were followed. PubMed/MEDLINE and Scopus were searched on 17 July 2023. The Newcastle-Ottawa Scale tool was used to assess the risk of bias. The protocol was pre-registered in PROSPERO (registration number: CRD 42023444368). Heterogeneity was assessed using the I2 test. Publication bias was assessed by visual inspection of the funnel plot and by Egger's regression asymmetry test. The final effect size was reported as OR or HR, depending on the study design of the included studies. RESULTS: Out of 682 records, 21 were included in the analysis. The pooled OR was 0.89 (95% CI = 0.84-0.94) based on 65,955 participants (I2 = 69.94). When only cohort studies were included, HR was 0.84 (95% CI = 0.76-0.94) based on 55,205 participants (I2 = 89.70). When only Alzheimer Disease was considered OR was 0.73 (95% CI = 0.62-0.85) based on 38,292 participants (I2 = 63.85). DISCUSSION: Despite the relatively low risk reduction associated with higher adherence to MedDiet among elderly, it should be considered that this population is the most affected. CONCLUSIONS: Adherence to MedDiet could be an effective non-pharmacological measure to reduce the burden of dementia, even among elderly.

Climate Change Perception and Mental Health. Results from a Systematic Review of the Literature.

Climate change is one of the main global challenges and influences various aspects of human health. Numerous studies have indeed demonstrated an association between extreme climate-related events and physical and mental health outcomes, but little is still known about the association between the perception/awareness of climate change and mental health. In accordance with the PRISMA 2020 guidelines, a search was conducted on PubMed and Scopus. The protocol was registered on PROSPERO. The included studies were original observational studies published in English, reporting the association between the perception/awareness of climate change and mental health. A total of 3018 articles were identified. A total of 10 observational studies were included. The period covered in the included studies ranged between 2012 and 2022. Climate change perception is consistently associated with adverse mental health effects across different types of estimates. In particular, the studies identified an association between a higher level of perception/awareness of climate change and depression, anxiety, eco-anxiety, stress, adjustment disorder, substance use, dysphoria, and even thoughts of suicide. Qualitative data underscore the impact on daily activities, contributing to feelings of loss and suicidal ideation. Moreover, climate change perception correlates with lower well-being and resilience. The association between awareness of climate change and mental health is a complex and still poorly explored phenomenon. The main limitations are the high heterogeneity in terms of exposure assessment and data reporting, which hinders quantitative analysis. These results show that climate change perception impacts mental health. Better understanding the phenomenon represents an opportunity to inform public health interventions that promote mental well-being.

Why Treat Patients with a Major Orthopaedic Surgery Only to Send Them Back to the Vulnerable Conditions That Made Them Sick in the First Place? A Conceptual Scenario to Improve Patient's Journey.

Individuals with severe cartilage degeneration of the hip or knee or collapsed vertebrae that cause spine deformities can suffer from joint and neuropathic pain in the back, disuse of the affected limb, and restriction of movements. Surgical intervention is the most widespread and successful solution to date. There is a general belief that eating healthy and staying physically and mentally active might have a preventive role against musculoskeletal disease occurrence, while instead, we are more certain of the benefits deriving from a healthy diet and exercise therapy after major orthopaedic procedures. These aspects are in fact vital components in enhanced recovery after surgery programmes. However, they are applied in hospital settings, are often centre-dependent, and lack primary and tertiary preventive efficacy since end once the patient is discharged. There is the lack of initiatives at the territorial level that ensure a continuum in the patient's journey towards orthopaedic surgery, home transition, and a healthy and long-lasting life. The expert panel advocates the integration of an intermediate lifestyle clinic that promotes healthy eating, physical activity, and sleep hygiene. In this facility directed by professionals in enhancing recovery after surgery, patients can be referred after the surgical indication and before home discharge. Surgery is in fact a moment when individuals are more curious to do their best to heal and stay healthy, representing a timepoint and opportunity for educating patients on how lifestyle changes may optimise not only their surgical recovery but also long-term future health state.

Rolling e-learning: an educational model to support Italian healthcare professionals during the COVID-19 pandemic.

BACKGROUND AND AIM: Rolling reviews have been widely used by the scientific community during the COVID-19 pandemic to provide guidelines and identify potential treatments in such a quickly evolving emergency. Throughout the two pandemic years, we provided independent and continuously updated (rolling) e-learning courses on COVID-19 targeted to Italian healthcare professionals with the aim of increasing dissemination based on the emerging evidence. The results of this project are presented in this brief report. METHODS: We launched five main courses on COVID-19 - with focus on treatments and vaccines - from February 2020 to December 2022. For each course, we collected and analised participation data and, via questionnaires, customer-satisfaction data on relevance, quality, efficacy and sponsor perception. RESULTS: From 22 February 2020 to 31 December 2022, a total of 224,459 enrollments were registered over the five courses with 192,966 passes (86%), for which Continuing Medical Education (CME) credits were awarded. Over 94% of participants considered the contents of high quality, relevant and effective for their educational needs. The absence of sponsorship perception, 83% overall, decreased relevantly for the two courses on COVID-19 vaccines (68.3%). CONCLUSIONS: Italian healthcare professionals working during the pandemic overwhelmingly appreciated and valued the rolling e-learning offer aimed at widening the dissemination of the best practices on COVID-19. This educational model provides independent, evidence-based and tailored information with the undoubted advantages of time flexibility, remote participation and continuous update, all elements that make it a useful tool in a pandemic as well as in a post-pandemic era.

Implementation of a centralized discharge planning office during the COVID-19 pandemic: translating the experience from the emergency to routine clinical practice.

Background and aim During the COVID-19 emergency, the lombardy region (northern Italy) implemented a regional Centralized Discharge Planning Office (CDPO) to promptly manage the discharge requests, rapidly match the needs of discharge hospitals with the availability of admission facilities and ensure the management of the entire discharge process. To improve the discharge process in routine clinical practice, maintaining the role of the CDPO could be of great interest. This paper describes the experience of the CDPO during the COVID-19 pandemic and discusses the possibility to translate this operational model to routine clinical practice. METHODS: The PRIAMO web portal was developed to manage discharge requests with centralized and standardized procedures. The activity on PRIAMO consisted of three stages: discharge request, sorting process, and discharge follow-up phase. To evaluate the activity of the CDPO, these indicators were considered: average time (hours) between patient discharge and transfer acceptance; average time (hours) between patient discharge and effective admission to the new facility; percentage of transfers whose destination was found directly by the CDPO; percentage of reallocations beyond 24 hours; mean distance between discharge and admission facilities. RESULTS: Process indicator evaluation showed a great reduction in the time between the discharge and the admission to post-acute care facilities. Transfers whose destination was found directly by the CDPO progressively increased. Reallocations beyond 24 hours by the CDPO decreased, suggesting an improvement in the quality of the operations. CONCLUSIONS: Centralized discharge planning has enabled timely and efficient management of discharge requests even in the moment of a surge, saving time and costs for acute care hospitals.

Congenital Cytomegalovirus and Hearing Loss: The State of the Art.

In developed countries, congenital cytomegalovirus (cCMV) infection is the most common congenital viral infection, representing the leading non-genetic cause of sensorineural hearing loss (HL). Diagnosis of cCMV infection can be performed by detection of CMV DNA in urine or saliva within 2-3 weeks after birth, or later in dried blood samples on the Guthrie card. Currently, there are many controversies regarding the preventive, diagnostic, and therapeutic approaches to cCMV infection. HL secondary to cCMV is highly variable in onset, side, degree, audiometric configuration, and threshold changes over time. Therefore, it is of paramount importance to perform a long and thorough audiological follow-up in children with cCMV infection to ensure early identification and prompt treatment of progressive and/or late-onset HL. Early cochlear implantation appears to be a valid solution not only for children with bilateral profound HL, but also for those with single-sided deafness, improving localization ability and understanding speech in noisy environments. Moreover, the decision to apply a unilateral cochlear implant in children with cCMV is strengthened by the non-negligible possibility of hearing deterioration of the contralateral ear over time.

SIMED-New Doc course, a matter of reflection.

BACKGROUND AND AIM: Obtaining a degree in medicine in Italy qualifies for the medical profession; this fact has entailed a newly qualified doctor's remarkable involvement on the medical activities of the National Health Service, especially during the Covid-19 pandemic. It is important to understand the knowledge of the newly qualified doctors and to create specific courses oriented to them. The aim of the study is to evaluate the impact of a peer learning course for the students who attend the last year of medicine school, with the purpose of defining the formal requests to integrate on the course. METHODS: A pre and post qualitative research has been carried out on SIMED-NEWDOC course. The course consisted on peer teaching lectures, as lecturers were resident doctors part of SIMED board. At the end of the course it has been submitted a survey to the participants, and data has been analyzed. RESULTS: The students enrolled were 139, the average of the participants was 27% of the registered. A qualitative evaluation questionnaire was submitted, the responses were 32 (86%). Average age was 25. Participants attending the last year of medicine school were 30 (95%). 40% of them declared to have attended at least 5 lessons. Among the course participants, 96% judged the course as very useful. CONCLUSIONS: All questionnaire results are useful to reflect on future projects. It is necessary to implement further educational projects to better understand the phenomenon, considering the positive impact that participants declared.

Perioperative adverse events in adult and pediatric spine surgery: A prospective cohort analysis of 364 consecutive patients.

Introduction: A precise knowledge of the possible Adverse Events (AEs) related to spinal surgical procedures is crucial in clinical practice. Research Question: Purposes of this study are: to determine the prevalence and severity of perioperative AEs associated with pediatric and adult spine surgery in a high volume center; to estimate the impact of perioperative AEs on length of hospital stay (LOS). Material and Methods: This is a prospective, observational, monocenter study, including 346 consecutive patients (294 adults and 52 pediatrics). The SAVES-V2 questionnaire was used to record AEs. The form was updated by the medical staff every time an adverse event was recorded during hospitalization. Results: 21,2% of pediatric patients and 20,7% of adults had at least 1 perioperative AEs. In adults, dural tear (3.1%) and neuropathic pain (4,8%), were the most frequent intraoperative and postoperative AE, respectively. In pediatric patients, neurologic deterioration was the most frequent postoperative AE. A diagnosis of deformity (p=0.01), an ASA grade equal or superior to 3 (p=0.023) and the procedure 'Posterior Spinal Fusion' (p=0.001) were associated with a higher frequency of AEs. AEs required prolonged LOS in 40 cases, 7 (70%) pediatric patients and 33 (65%) adults. Discussion and Conclusion: The overall prevalence of AEs is 20.8%, and, although the distribution is almost equal between adult and pediatric patients, their severity is related to age, being higher in pediatric patients. Deformities, deformity correction, revision surgery and AP surgery are the most impactful factors. AEs seriously affect hospitalization, with prolonged LOS (mean 6 days).

Durability of Humoral Responses after the Second Dose of mRNA BNT162b2 Vaccine in Residents of a Long Term Care Facility.

Residents of long-term care facilities (LTCFs) have been dramatically hit by the COVID-19 pandemic on a global scale as older age and comorbidities pose an increased risk of severe disease and death. The aim of the study was to assess the quantity and durability of specific antibody responses to SARS-CoV-2 after the first cycle (two doses) of BNT162b2 vaccine. To achieve this, SARS-CoV-2 Spike-specific IgG (S-IgG) titers was evaluated in 432 residents of the largest Italian LTCF at months 2 and 6 after vaccination. By stratifying levels of humoral responses as high, medium, low and null, we did not find any difference when comparing the two time points; however, the median levels of antibodies halved overtime. As positive nucleocapsid serology was associated with a reduced risk of a suboptimal response at both time points, we conducted separate analyses accordingly. In subjects with positive serology, the median level of anti-S IgG slightly increased at the second time point, while a significant reduction was observed in patients without previous exposure to the virus. At month 6, diabetes alone was associated with an increased risk of impaired response. Our data provide additional insights into the longitudinal dynamics of the immune response to BNT162b2 vaccination in the elderly, highlighting the need for SARS-CoV-2 antibody monitoring following third-dose administration.

Sero-survey on long-term care facility residents reveals increased risk of sub-optimal antibody response to BNT162b2: implications for breakthrough prevention.

BACKGROUND: The impact of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on residents of long-term care facilities (LTCFs) has been dramatic on global scale as older age and comorbidities pose an increased risk of severe disease and death. METHODS: Aim of this study was to evaluate SARS-CoV-2 Spike-specific IgG (S-IgG) antibody titers in 478 residents and 649 health care workers of a large Italian long-term care facility two months after complete vaccination with BNT162b2. Associations among resident-related factors and predictors of humoral response were investigated. RESULTS: By stratifying levels of humoral responses, we found that 62.1%, 21.6%, 12.1% and 4.2% of residents had high (>1,000 BAU/ml), medium (101-1,000), low (1-100) and null (<1 BAU/mL) S-IgG titers, respectively. Residents with documented previous COVID-19 and those with SARS-CoV-2 nucleocapsid-specific IgG (N-IgG) positive serology showed higher level of serological response, while significant associations were observed for cancer with suboptimal response (p = 0.005) and the administration of corticosteroid for suboptimal response (p = 0.028) and a null one (p = 0.039). According to multivariate logistic regression, predictors of an increased risk of null response were advanced age (Odd ratio, OR: 2.630; Confidence interval, CI: 1.13-6.14; p = 0.025), corticosteroid therapy (OR: 4.964; CI: 1.06-23.52; p = 0.042) and diabetes mellitus (OR:3.415; CI:1.08-10.8; p = 0.037). In contrast, previous diagnosis of COVID-19 was strongly associated with a reduced risk of null response to vaccination (OR:0.126; CI:0.02-0.23; p < 0.001). CONCLUSIONS: SARS-CoV-2 specific antibodies in elderly individuals should be consider when deciding the need of a third dose of vaccine for prevention of reinfections in LTCFs despite the maintenance of barrier measures.

Mast Cell Cytokines IL-1, IL-33, and IL-36 Mediate Skin Inflammation in Psoriasis: A Novel Therapeutic Approach with the Anti-Inflammatory Cytokines IL-37, IL-38, and IL-1Ra.

Psoriasis (PS) is a skin disease with autoimmune features mediated by immune cells, which typically presents inflammatory erythematous plaques, and is associated with many comorbidities. PS exhibits excessive keratinocyte proliferation, and a high number of immune cells, including macrophages, neutrophils, Th1 and Th17 lymphocytes, and mast cells (MCs). MCs are of hematopoietic origin, derived from bone marrow cells, which migrate, mature, and reside in vascularized tissues. They can be activated by antigen-provoking overexpression of proinflammatory cytokines, and release a number of mediators including interleukin (IL)-1 and IL-33. IL-1, released by activated keratinocytes and MCs, stimulates skin macrophages to release IL-36-a powerful proinflammatory IL-1 family member. IL-36 mediates both innate and adaptive immunity, including chronic proinflammatory diseases such as psoriasis. Suppression of IL-36 could result in a dramatic improvement in the treatment of psoriasis. IL-36 is inhibited by IL-36Ra, which binds to IL-36 receptor ligands, but suppression can also occur by binding IL-38 to the IL-36 receptor (IL-36R). IL-38 specifically binds only to IL-36R, and inhibits human mononuclear cells stimulated with IL-36 in vitro, sharing the effect with IL-36Ra. Here, we report that inflammation in psoriasis is mediated by IL-1 generated by MCs-a process that activates macrophages to secrete proinflammatory IL-36 inhibited by IL-38. IL-37 belongs to the IL-1 family, and broadly suppresses innate inflammation via IL-1 inhibition. IL-37, in murine models of inflammatory arthritis, causes the suppression of joint inflammation through the inhibition of IL-1. Therefore, it is pertinent to think that IL-37 can play an inhibitory role in inflammatory psoriasis. In this article, we confirm that IL-38 and IL-37 cytokines emerge as inhibitors of inflammation in psoriasis, and hold promise as an innovative therapeutic tool.

Lacticaseibacillus paracasei DG enhances the lactoferrin anti-SARS-CoV-2 response in Caco-2 cells.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing the ongoing global pandemic of coronavirus disease 2019 (COVID-19), which primarily manifests with respiratory distress and may also lead to symptoms associated with the gastrointestinal tract. Probiotics are living microorganisms that have been shown to confer immune benefits. In this study, we investigated the immunomodulatory effects and anti-SARS-CoV-2 activity of three different Lacticaseibacillus probiotic strains, either alone or in combination with lactoferrin, using the intestinal epithelial Caco-2 cell line. Our results revealed that the Lacticaseibacillus paracasei DG strain significantly induced the expression of genes involved in protective antiviral immunity and prevented the expression of proinflammatory genes triggered by SARS-CoV-2 infection. Moreover, L. paracasei DG significantly inhibited SARS-CoV-2 infection in vitro. L. paracasei DG also positively affected the antiviral immune activity of lactoferrin and significantly augmented its anti-SARS-CoV-2 activity in Caco-2 intestinal epithelial cells. Overall, our work shows that the probiotic strain L. paracasei DG is a promising candidate that exhibits prophylactic potential against SARS-CoV-2 infection.

Protective Effects of Lactoferrin against SARS-CoV-2 Infection In Vitro.

SARS-CoV-2 is a newly emerging virus that currently lacks curative treatments. Lactoferrin (LF) is a naturally occurring non-toxic glycoprotein with broad-spectrum antiviral, immunomodulatory and anti-inflammatory effects. In this study, we assessed the potential of LF in the prevention of SARS-CoV-2 infection in vitro. Antiviral immune response gene expression was analyzed by qRT-PCR in uninfected Caco-2 intestinal epithelial cells treated with LF. An infection assay for SARS-CoV-2 was performed in Caco-2 cells treated or not with LF. SARS-CoV-2 titer was determined by qRT-PCR, plaque assay and immunostaining. Inflammatory and anti-inflammatory cytokine production was determined by qRT-PCR. LF significantly induced the expression of IFNA1, IFNB1, TLR3, TLR7, IRF3, IRF7 and MAVS genes. Furthermore, LF partially inhibited SARS-CoV-2 infection and replication in Caco-2 intestinal epithelial cells. Our in vitro data support LF as an immune modulator of the antiviral immune response with moderate effects against SARS-CoV-2 infection.

Preliminary Analysis of Relationships between COVID19 and Climate, Morphology, and Urbanization in the Lombardy Region (Northern Italy).

The coronavirus disease 2019 (COVID-19) pandemic is the most severe global health and socioeconomic crisis of our time, and represents the greatest challenge faced by the world since the end of the Second World War. The academic literature indicates that climatic features, specifically temperature and absolute humidity, are very important factors affecting infectious pulmonary disease epidemics - such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS); however, the influence of climatic parameters on COVID-19 remains extremely controversial. The goal of this study is to individuate relationships between several climate parameters (temperature, relative humidity, accumulated precipitation, solar radiation, evaporation, and wind direction and intensity), local morphological parameters, and new daily positive swabs for COVID-19, which represents the only parameter that can be statistically used to quantify the pandemic. The daily deaths parameter was not considered, because it is not reliable, due to frequent administrative errors. Daily data on meteorological conditions and new cases of COVID-19 were collected for the Lombardy Region (Northern Italy) from 1 March, 2020 to 20 April, 2020. This region exhibited the largest rate of official deaths in the world, with a value of approximately 1700 per million on 30 June 2020. Moreover, the apparent lethality was approximately 17% in this area, mainly due to the considerable housing density and the extensive presence of industrial and craft areas. Both the Mann-Kendall test and multivariate statistical analysis showed that none of the considered climatic variables exhibited statistically significant relationships with the epidemiological evolution of COVID-19, at least during spring months in temperate subcontinental climate areas, with the exception of solar radiation, which was directly related and showed an otherwise low explained variability of approximately 20%. Furthermore, the average temperatures of two highly representative meteorological stations of Molise and Lucania (Southern Italy), the most weakly affected by the pandemic, were approximately 1.5 °C lower than those in Bergamo and Brescia (Lombardy), again confirming that a significant relationship between the increase in temperature and decrease in virulence from COVID-19 is not evident, at least in Italy.

Disentangling the Hypothesis of Host Dysosmia and SARS-CoV-2: The Bait Symptom That Hides Neglected Neurophysiological Routes.

The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. The full-blown COVID-19 can lead, in susceptible individuals, to premature death because of the massive viral proliferation, hypoxia, misdirected host immunoresponse, microthrombosis, and drug toxicities. Alike other coronaviruses, SARS-CoV-2 has a neuroinvasive potential, which may be associated with early neurological symptoms. In the past, the nervous tissue of patients infected with other coronaviruses was shown to be heavily infiltrated. Patients with SARS-CoV-2 commonly report dysosmia, which has been related to the viral access in the olfactory bulb. However, this early symptom may reflect the nasal proliferation that should not be confused with the viral access in the central nervous system of the host, which can instead be allowed by means of other routes for spreading in most of the neuroanatomical districts. Axonal, trans-synaptic, perineural, blood, lymphatic, or Trojan routes can gain the virus multiples accesses from peripheral neuronal networks, thus ultimately invading the brain and brainstem. The death upon respiratory failure may be also associated with the local inflammation- and thrombi-derived damages to the respiratory reflexes in both the lung neuronal network and brainstem center. Beyond the infection-associated neurological symptoms, long-term neuropsychiatric consequences that could occur months after the host recovery are not to be excluded. While our article does not attempt to fully comprehend all accesses for host neuroinvasion, we aim at stimulating researchers and clinicians to fully consider the neuroinvasive potential of SARS-CoV-2, which is likely to affect the peripheral nervous system targets first, such as the enteric and pulmonary nervous networks. This acknowledgment may shed some light on the disease understanding further guiding public health preventive efforts and medical therapies to fight the pandemic that directly or indirectly affects healthy isolated individuals, quarantined subjects, sick hospitalized, and healthcare workers.

Changes of clinical activities in an orthopaedic institute in North Italy during the spread of COVID-19 pandemic: a seven-week observational analysis.

PURPOSE: The COVID-19 pandemic is importantly affecting the orthopaedic practice all over the world with Northern Italy being the first European area that faced the worst scenario. In this study, the changes in clinical practice occurred in an orthopaedic center in Milan are described. METHODS: Number and type of admissions, outpatients cancelled and preserved, emergency room, and intensive care unit activities have been analyzed in the timeframe of seven weeks since the beginning of the pandemic (from February 24th to April 10th) and compared with the same period in 2019. RESULTS: The planned surgical admissions declined from 2172 in 2019 to 664 in 2020 (69.42%, p < 0.0001), while emergencies increased from 158 to 268 (69.62%). The rehabilitation admissions declined from 414 to 69 (83.33%). The overall admission decreased by 63.52%, the trend showed a drop in the last weeks. Surgery performed in the COVID-19 operating room increased by 16.7% in the last week. Seven deaths occurred (0.7% of all orthopaedics and trauma admissions) compared with four (0.1%) which happened in the same period in 2019 (p = 0.004). Six of these patients were suffering from COVID-19. A total of 23,580 outpatients (93.8%) were cancelled. Emergency room consultations declined by 68.14% and 63.47% among white and green priority, respectively, while increased by 25% and 100% among yellow and red, respectively. CONCLUSION: These numbers show the radical changed scenario in an orthopaedic center in Milan during COVID-19 pandemic. Elective surgery declined rapidly going close to zero, outpatient admissions were restricted to cases that cannot be postponed, while emergencies increased due to the role played by the hospital as referral orthopaedic centre during the pandemic. The still ongoing emergency will have important impacts on the overall orthopaedic healthcare management for the next months.