University Hospital In Milan Research Articles

Clinical Presentations of Parvovirus B19: A Case Series.

Parvovirus B19 (PVB19) is a small, nonenveloped, single-stranded DNA virus commonly causing asymptomatic infections or mild, flu-like symptoms. In children, PVB19 can lead to various clinical conditions, including erythema infectiosum, arthropathy, transient aplastic crisis and papular-purpuric eruptions, among others. We present 3 pediatric cases treated at Luigi Sacco University Hospital in Milan, Italy, in March 2024, each demonstrating distinct manifestations of PVB19 infection. Case 1 involved a 7-year-old girl with a maculopapular rash and panniculitis-like symptoms. Case 2 described an 8-year-old boy with a maculopapular rash, vasculitis component and mild thrombocytopenia. Case 3 focused on a 7-year-old girl with petechial and purpuric eruptions and a mild decrease in platelets. Serological tests confirmed PVB19 infection in all cases. The discussed cases highlight the heterogeneous clinical spectrum of PVB19 infection and emphasize its potential to cause thrombocytopenia even in healthy children. The recent surge in PVB19 cases in Europe, aligned with known epidemiological cycles, underscores the importance of vigilance in diagnosis, particularly during peak seasons. Additionally, concerning the role of serological testing in the diagnostic process, the potential for cross-reactivity among viral antigens is pointed out. PVB19 is a common infection with a broad range of clinical presentations. Awareness of its potential complications, including thrombocytopenia, even in nonimmunocompromised children, is crucial. Moreover, understanding the epidemiological patterns of PVB19 can aid in anticipating and managing outbreaks, thus minimizing its impact on pediatric health.

Mental Disorders Among Healthcare Students Attending a Large University Hospital in Milan, Italy.

The high incidence rates, treatment difficulties, and tendency to become chronic, which subsequently affects personal and occupational functioning, make mental health disorders among the most important public health concerns. In this context, healthcare university students (HS) appear to be more vulnerable to psychological distress than others. Investigate the prevalence of diagnosed mental illness among different groups of HS to detect students who may be psychologically vulnerable and determine whether the implementation of support interventions is necessary. All HS who had a clinical examination performed by an occupational physician at our occupational health unit between 2021 and 2022 were included in our case series. Data were collected and analyzed as part of the occupational physicians' health surveillance program. out of 679 HS (507 females, 172 males, aged 22.2±3.9 mean±s.d) undergone clinical examination at our Occupational Health Unit, 36 (5.3%) reported a diagnosed psychiatric illness, and 20 were receiving pharmacological therapy at the time of the visit. A higher prevalence of psychological disorders has been highlighted in females (6.1% vs 2.9% in males) and students of the mental health sector (11.1%) when compared with others. A fit-to-work judgment with prescription was necessary for 16.7% of students with mental diseases. The presence of psychiatric disorders was associated with underweight (27.8%) and higher smoking habit (44.4%). These results underline the necessity of improving the current health surveillance protocols, which should also evaluate students' psychological fragility and implement effective intervention strategies to promote their health and wellbeing.

Early-onset obsessive-compulsive disorder: sociodemographic and clinical characterization of a large outpatient cohort

IntroductionObsessive-compulsive disorder (OCD) is a prevalent and disabling condition characterized by a wide variety of phenotypic expressions. Several studies have reinforced the hypothesis of OCD heterogeneity by proposing subtypes based on predominant symptomatology (Mataix-Cols et al., 2005), course (Tukel et al., 2007), and comorbidities (Mahasuar et al., 2011). Early-onset OCD could be considered a neurodevelopmental subtype of OCD, with evidence of distinct neurocircuits supporting disease progression (Park et al., 2022).ObjectivesThe aim of the present study is to evaluate the sociodemographic and clinical differences between the early-onset and late-onset subtypes in a large patient cohort.MethodsTwo hundred and eighty patients diagnosed with OCD were consecutively recruited from the OCD Tertiary Clinic at Luigi Sacco University Hospital in Milan. Sociodemographic and clinical variables were analyzed for the entire sample and compared between the two subgroups (EO: early-onset, age <18 years [40%]; LO: late-onset, age ≥ 18 years [60%]).ResultsThe EO group showed a higher frequency of male gender (65.5% vs 34.5%, p< .001, see Figure 1a), a higher presence of lifetime psychiatric comorbidities (75.7% vs 24.3%, p =.025), and higher rates of Tic and Tourette disorders (7.2% vs 0%, p=.006) compared to the LO group. Additionally, in the EO subgroup, a longer duration of untreated illness was observed (9.05 ± 10.0 vs 5 ± 7.17; p<.001, see Figure 1b), along with a lower presence of insight (33.3% vs. 66.7%, p =.024). No significant differences emerged in the Yale-Brown Obsessive-Compulsive Scale scores between the groups.Image:Image 2:ConclusionsThe early-onset OCD subtype highlights a more severe psychopathological profile compared to the late-onset group. Exploring distinct manifestations and developmental trajectories of OCD can contribute to a better definition of homogeneous subtypes, useful for studying risk factors and defining targeted therapeutic strategies for treatment.Disclosure of InterestB. Benatti Speakers bureau of: Angelini, Lundbeck, Janssen, Rovi, N. Girone: None Declared, M. Vismara: None Declared, C. Bucca: None Declared, B. Dell’Osso Grant / Research support from: Angelini, Lundbeck, Janssen, Pfizer, Otzuka, Neuraxpharm, and Livanova, Speakers bureau of: Angelini, Lundbeck, Janssen, Pfizer, Otzuka, Neuraxpharm, and Livanova.

Analysis and clinical determinants of post-COVID-19 syndrome in the Lombardy region: evidence from a longitudinal cohort study

ObjectiveTo define macro symptoms of long COVID and to identify predictive factors, with the aim of preventing the development of the long COVID syndrome.DesignA single-centre longitudinal prospective cohort study conducted...

Detection and typization of HPV genotypes in subjects with oral and upper respiratory tract lesions, Milan, Italy

Background Oral human papillomavirus (HPV) is common among healthy individuals but causes and implications of persistent infections are under evaluation in the pathogenesis of head and neck neoplasms. Methods This was a retrospective study evaluating the prevalence of high-risk (HR), probable HR and low-risk (LR) HPV types in patients reporting signs/symptoms of oral and upper respiratory tract lesions. Individuals attending between 2019 and 2022 a University Hospital in Milan, Italy, with risk factors for HPV (unprotected oral sex and/or previous documentation of HPV infection in oral and upper respiratory tract and/or another anatomical site) were included. Results Fourteen out of 110 (12.7%) individuals tested positive for HPV DNA. The prevalence of HR-HPV and LR-HPV was 3.6% (4/110) and 9.1% (10/110), respectively. No probable/possible HR-HPV was detected. Specifically, 10/110 (9.1%) were diagnosed with 1 LR-HPV genotype, 3/110 (2.7%) were infected with 1 HR-HPV and 1/110 had 3 concomitant HR-HPV types. HPV 16 (2.7%, 3/110) and 6 (4.5%, 5/110) were the most common HR and LR types, respectively. One patient positive for HPV 16, 33 and 35 was diagnosed with cancer at the base of the tongue. Two individuals among those who tested positive for HPV DNA reported previous HPV vaccination. Conclusions Our data, in line with observations from previous prevalence studies, support the potential role of HPV in head and neck neoplasms. HPV DNA testing should be performed in patients presenting lesions in oral/respiratory tracts and risk factors for HPV. Improvement in HPV vaccination coverage is warranted.

Air pollution exposure, SARS-CoV-2 infection, and immune response in a cohort of healthcare workers of a large university hospital in Milan, Italy

Several studies have examined the possible relationship between air pollutants and the risk of COVID-19 but most returned controversial findings. We tried to assess the association between (short- and long-term) exposure to particulate and gaseous pollutants, SARS-CoV-2 infections, and immune response in a population of healthcare workers (HCWs) with well-characterized individual data. We collected occupational and clinical characteristics of all HCWs who performed a nasopharyngeal swab (NPS) for detecting SARS-CoV-2 at the Policlinico Hospital in Milan (Lombardy, Italy) between February 24, 2020 (day after first documented case of COVID-19 in our hospital) and December 26, 2020 (day before start of the vaccination campaign). Each subject was assigned daily average levels of particulate matter ≤10 μm (PM10), nitrogen dioxide (NO2), and ozone (O3) retrieved from the air quality monitoring station closest to his/her residential address. Air pollution data were treated as time-dependent variables, generating person-days at risk. Multivariate Poisson regression models were fit to evaluate the rate of positive NPS and to assess the association between air pollution and antibody titer among NPS-positive HCWs. Among 3712 included HCWs, 635 (17.1%) had at least one positive NPS. A 10 μg/m3 increase in NO2 average concentration in the four days preceding NPS was associated with a higher risk of testing positive [Incidence Rate Ratio (IRR) = 1.08, 95% confidence interval (CI): 1.01; 1.16)]. When considering a 1 μg/m3 increase in 2019 annual NO2 average, we observed a higher risk of infection (IRR: 1.02, 95%CI: 1.00; 1.03) and an increased antibody titer (+2.4%, 95%CI: 1.1; 3.6%). Findings on PM10 and O3 were less consistent and, differently from NO2, were not confirmed in multipollutant models. Our study increases the body of evidence suggesting an active role of air pollution exposure on SARS-CoV-2 infection and confirms the importance of implementing pollution reduction policies to improve public health.

Editorial introductions.

Editorial introductions.

The impact of lifestyle on adherence to treatment in a sample of patients with Major Depression

IntroductionPoor adherence to treatment is currently stated to be one of the causes of depression relapse and recurrence.ObjectivesAim of the present study was to assess potential differences in terms of clinical and socio-demographic characteristics specifically related to adherence to treatment features, medical comorbidities, and substance abuse in a sample of patients diagnosed with Major Depression in an Italian psychiatric department.MethodsPatients with a DSM-5 diagnosis of Unipolar or Bipolar Major Depressive Episode, of either gender or any age were recruited from the Psychiatry Department of Luigi Sacco University Hospital in Milan. Main clinical and socio-demographic variables were collected reviewing patients’ medical records. Moreover, adherence to psychopharmacological treatment was assessed using the Clinician Rating Scale (CRS; Kemp et al, 1996; 1998). Adherence was defined as ratings of > or =5 on the CRS. Descriptive and association analyzes were performed, setting the significance level at p<.05.Results80 patients with a diagnosis of Unipolar Major depressive episode (48.9%) and Bipolar Major Depressive Episode (51.1%) were included. For the purposes of the study, the total sample was divided into two subgroups based on adherence to pharmacological treatment (A+ vs A-). Significantly higher rates of inpatients from psychiatric ward were A- compared to A+ patients (84.6% vs 48.1%, p=.011). A- patients were significantly more unemployed (57.9% vs 23.8%, p=.015), were mostly living in their family of origin (50% vs 21.4%, p=.027), and had fewer years of education compared to A+ subgroup (10.52±3.28 vs 12.2±3.1 years, p=.053). Higher rates of Bipolar Depression diagnosis and a prevalent manic polarity lifetime emerged in A- compared to the A+ group (73.1% vs 42.3%, p=.010; 30.8% vs 3%, p=.011, respectively). Moreover, A+ reported significantly higher rates of depressive prevalent polarity lifetime (72.7% vs 30.8%, p=.011). A- reported significantly higher rates of comorbidity with alcohol or other substance use disorders lifetime (46.2% vs 5.7%, p=.006) and almost one involuntary commitment lifetime (23.1% vs 11.1%, p=.013).ConclusionsIn our sample adherence to treatments showed significant differences in terms of clinical and socio-demographic characteristics. Low levels of adherence have been associated with higher hospitalization rates, involuntary commitments, greater comorbidity with alcohol or drugs. Our data therefore seem to suggest that less adherence leads to a worse disease course and a worse quality of life. It therefore appears useful to include an assessment of adherence in the clinical practice and implement interventions to improve therapeutic adherence and ensure a better quality of life.Disclosure of InterestNone Declared

Liver resection of hepatocellular carcinoma in HIV-HCV co-infected patients: a retrospective case series

IntroductionDespite the effectiveness of new therapies and awareness campaigns, the number of seropositive patients is increasing every year. Recently, other causes of death, not directly related to HIV, have emerged, such as chronic liver disease. The risk of hepatocellular carcinoma (HCC) is seven times greater in HIV patients than in noninfected patients, and it is especially attributable to HCV infection. The aim of our study was to evaluate clinical outcomes of HCC in HIV-HCV co-infected patients after liver resection (LR).Materials and methodsThe current study was conducted on a prospective database and reviewed retrospectively. All consecutive patients with HCC treated by LR from January 2013 to March 2019 at the Luigi Sacco University Hospital in Milan were enrolled. We included patients older than 18 years of age with HCV-related HCC, and in this set of patients, we identified two groups based on the presence of HIV infection.ResultsWe identified 16 patients with HCV infection and precisely five with HIV-HCV co-infection and eleven with HCV infection alone. All HIV patients were male against 72.7% in the non-HIV group (p = 0.509). All patients had optimal HIV virologic control and a normal CD4 T-cell count. The mean diagnosis-to-treatment interval was statistically different between the two groups (HIV versus non-HIV: 1.2 ± 0.55 months versus 2.39 ± 1.09 months, p = 0.039).No other significant differences were found between HIV-HCV co-infected patients and HCV-infected patients. Long-term outcomes in terms of OS and RFS were similar between the two groups.ConclusionsWith a multidisciplinary approach and intensive support, LR can be a safe and efficacious procedure in HIV-HCV patients. For these reasons, we should not exclude potential patients merely on the basis of their HIV seropositivity.

P-425 Premature follicular-phase progesterone increase in ART cycles and endometrial receptivity: evaluation of new, more reliable predictors

Abstract Study question Is plasma Progesterone (P) at HCG administration more sensitive in predicting endometrial receptivity in fresh IVF cycles than PFI (progesterone-follicles index) and POI (progesterone-oocytes index)? Summary answer Our data suggest that POI predicts endometrial receptivity defect better than the P assay alone, thus allowing better decision making. What is known already The premature increase in plasma P in the follicular phase of stimulated IVF cycles has been associated with a lower embryo implantation rate because of reduced endometrial receptivity. There is still no consensus on how this impediment to implantation should occur and what threshold should be used. Moreover,since the efficacy of P increase in conditioning reproductive outcomes is more intense in patients with normo- and poor-response and generally inversely proportional to the ovarian response to stimulation, PFI and POI, which better reflect the average amount of P secreted from the follicles, have been suggested as potential additional markers of receptivity. Study design, size, duration Retrospective analysis of fresh IVF-ET cycles. PFI was obtained dividing the plasma P level on the day of hCG administration by the number of follicles ≥14 mm; POI by the number of oocytes retrieved. Pearson correlations, ROC curves, multivariate logistic regression analysis and Cox regression were performed to evaluate the predictive value of PFI and POI for the main outcomes we considered: ongoing pregnancy rate (OPR) and live birth rate (LBR). Participants/materials, setting, methods Women undergoing IVF cycles at San Paolo University Hospital in Milan between 2016 and 2021 were enrolled. As exclusion criteria, we considered previous ovarian surgery, endometriosis, severe male factor and cycle interruption before the embryo transfer. We collected the following data: age of the woman; stimulation protocol; total amount of FSH administered; P and Estradiol (E2) levels and number of follicles >14 mm on induction day; number of oocytes collected; OPR and LBR. Main results and the role of chance A total of 662 fresh embryo transfers (ETs) were performed and 214 pregnancies were achieved. We observed a statistically significant difference in age, number of total embryos and POI between women who became pregnant and those who did not. Specifically, Pearson’s correlation revealed a significant positive correlation between pregnancy and number of total embryos (r = 0.165, p < 0.001), and a significant negative correlation between pregnancy and age (r = 0.201, p < 0.001) and POI (r=-0.096, p = 0.013). Multivariate logistic regression revealed POI to be the most significant predictive parameter of pregnancy, with a odds ratio of 4.374 (p = 0.007, CI: 1.496-12.797). The ROC curve confirmed the highest predictive value of POI for OPR. Finally, Cox regression showed that POI <0.18 was correlated with better OPR (odds ratio=1.419, p = 0.012), suggesting the potential clinical impact of identifying an optimal cut-off of POI to reconsider patient management. Limitations, reasons for caution The results of this study are limited by the small population size. Wider implications of the findings Since the effect on endometrial receptivity of increased plasma P is inversely proportional to ovarian response,we suggest using a marker that accounts for response characteristics. POI has been found to be a reliable index for predicting IVF-ET cycle outcomes,supporting a limit beyond which the fresh embryo transfer should be reconsidered. Trial registration number N/A

Effect of methylprednisolone treatment on COVID-19: An inverse probability of treatment weighting analysis.

ObjectivesWhile corticosteroids have been hypothesized to exert protective benefits in patients infected with SARS-CoV-2, data remain mixed. This study sought to investigate the outcomes of methylprednisone administration in an Italian cohort of hospitalized patients with confirmed SARS-CoV-2 infection.MethodsPatients with confirmatory testing for SARS-CoV-2 were retrospectively enrolled from a tertiary university hospital in Milan, Italy from March 1st to April 30th, 2020 and divided into two groups by administration of corticosteroids. Methylprednisolone was administered to patients not responding to pharmacological therapy and ventilatory support at 0.5-1mg/kg/day for 4 to 7 days. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences between the steroid and non-steroid cohorts via inverse probability of treatment weight. Primary outcomes included acute respiratory failure (ARF), shock, and 30-day mortality among surviving patients.ResultsAmong 311 patients enrolled, 71 patients received steroids and 240 did not receive steroids. The mean age was 63.1 years, 35.4% were female, and hypertension, diabetes, heart disease, and chronic pulmonary disease were present in 3.5%, 1.3%, 14.8% and 12.2% respectively. Crude analysis revealed no statistically significant reduction in the incidence of 30-day mortality (36,6% vs 21,7%; OR, 2.09; 95% CI, 1.18–3.70; p = 0.011), shock (2.8% vs 4.6%; OR, 0.60; 95% CI = 0.13–2.79; p = 0.514) or ARF (12.7% vs 15%; OR, 0.82; 95% CI = 0.38–1.80; p = 0.625) between the steroid and non-steroid groups. After IPTW analysis, the steroid-group had lower incidence of shock (0.9% vs 4.1%; OR, 0.21; 95% CI,0.06–0.77; p = 0.010), ARF (6.6% vs 16.0%; OR, 0.37; 95% CI, 0.22–0.64; p<0.001) and 30-day mortality (20.3% vs 22.8%; OR 0.86; 95% CI, 0.59–1.26 p = 0.436); even though, for the latter no statistical significance was reached. Steroid use was also associated with increased length of hospital stay both in crude and IPTW analyses. Subgroup analysis revealed that patients with cardiovascular comorbidities or chronic lung diseases were more likely to be steroid responsive. No significant survival benefit was seen after steroid treatment.ConclusionsPhysicians should avoid routine methylprednisolone use in SARS-CoV-2 patients, since it does not reduce 30-day mortality. However, they must consider its use for severe patients with cardiovascular or respiratory comorbidities in order to reduce the incidence of either shock or acute respiratory failure.

Incidence and predictive factors of non adherence to therapy in young adults attending a psycho social center in Milan: a retrospective observational “Real world” study

IntroductionNon adherence to psychotropic drugs is associated with negative outcomes, including hospitalizations, aggressive behaviors, suicide attempts and increased premature mortality. It represents a psychiatric challenge, especially in young adults who show higher risk of non-adherence to treatmentObjectivesFirstly this study evaluates the incidence of non-adherence to therapy in 18-24 years patients from a Psycho-Social Center in Milan; and then to analyze the predictive factors of non-adherence.MethodsIn this retrospective “Real Life” observational study, 120 outpatients aged 18 to 24 years, from Psycho-social Center of L. Sacco University Hospital in Milan, were recruited in 2019. Non-adherence to treatment, according to the World Health Organization, was considered “a modality of assuming medications that does not correspond to healthcare professionals’ recommendations”. Statistical analysis were performed with chi-square, ANOVA and linear regression tests, setting significance to p&lt;0.05.Results88 of 120 outpatients (73.3%) received an indication to psychopharmacological treatment. Of these, 23 (26.1%) did not show adherence to therapy. Results showed a positive association between non-adherence and increased hospitalizations (p &lt;.01), oral antipsychotics (p&lt;.05) and drop-out rates (p&lt;.001). A significant correlation was also observed between non-adherence and Intellectual Disability (p&lt;.05), Bipolar Disorder (p&lt;.05), psychotic symptoms (p&lt;.05), alterations in affectivity and mood (p&lt;.005), alterations in sleep pattern (p&lt;.05), school dropout (p&lt;.05) and poor family support (p&lt;.01).ConclusionsThis study confirms that non-adherence has a relevant incidence in young-adults psychiatric population, highlighting the importance of effective and structured assessment in clinical practice to identify predictive factors and risk profiles associated with this phenomenon.DisclosureNo significant relationships.

Mental health evaluation of patients with Inflammatory Bowel Disease and psychiatric comorbidities during the COVID-19 pandemic

IntroductionThe mental health of subjects with chronic medical illnesses, such as Inflammatory Bowel Disease (IBD- Crohn’s Disease and Ulcerative Colitis), is typically compromised and the current COVID-19 pandemic might have additionally increased this burden.ObjectivesThe aim of the present study was to investigate, during the COVID-19 pandemic, if the presence of a comorbid psychiatric disorder has played a role as an aggravating factor on mental health in patients with IBD.MethodsTwenty Five patients with psychiatric comorbidities (PC+) and twenty five without (PC-) comparable for age and gender, were recruited at the Gastroenterology department at Sacco University Hospital in Milan. Participants were assessed a psychiatric evaluation, collecting socio-demographic variables and measures of anxiety and depression [on the Hospital Anxiety Depression Scale (HADS)], sleep patterns [on the Insomnia Severity Index (ISI)] and general health status [on the Short Form Health Survey 36 (SF-36)].Comparative statistical analyses were performed with t test with Bonferroni correction.ResultsPC+ (n=25) showed more severe anxiety and depressive symptoms compared with PC- (n=25) (p &lt;.001) and worse sleep pattern (p&lt;.05). With respect to general health status, PC+ showed reduced physical activities (p&lt;.05), social activities (p&lt;.05), mental health (p&lt;.01) and role limitations due to physical health (p&lt;.05).ConclusionsThe present findings showed a worse mental health in subjects with IBD and psychiatric comorbidities during Covid-19 pandemic, highlighting the importance of screening and treatment of psychiatric symptoms disorders in these patients.DisclosureNo significant relationships.

Editorial introductions.

Editorial introductions.

COVID-19 and Influenza Vaccination Campaign in a Research and University Hospital in Milan, Italy

Background: Healthcare workers (HCWs) are a historical key target of influenza vaccination programs. For the 2021–2022 season, WHO considered the coadministration of a flu and a COVID-19 vaccine as acceptable and recommended it to allow for higher uptake of both vaccines. The aim of this study was to investigate demographic and occupational features of vaccinated HCWs, reasons behind flu vaccine acceptance and a possible effect of the coadministration of a COVID-19 vaccine, in order to potentially draw general conclusions on HCWs’ attitude towards flu vaccination and inform further strategies for consistent improvement of vaccine acceptance. Methods: a promotional and educational campaign, a gaming strategy, and vaccination delivery through both a large central hub and on-site ambulatories, were the implemented strategies. In the central hub, the flu/COVID-19 vaccine coadministration was offered. Statistical descriptive analysis, multiple correspondence analysis (MCA) and logistic regression models were performed. Results: 2381 HCWs received the flu vaccine, prompting a vaccination coverage rate (VCR) of 52.0% versus 43.1% in the 2020–2021 campaign. Furthermore, 50.6% vaccinated HCWs belonged to the 18–39 years-old age group. The most expressed reasons for vaccine uptake were “Vaccination is the most effective strategy of prevention” (n = 1928, 81.0%), “As HCW it’s my duty to get vaccinated to protect my patients” (n = 766, 32.2%), and the group of COVID-19-related reasons (n = 586, 24.6%). In addition, 23.3% HCWs received the flu vaccine in the current campaign but not in the previous one (newly vaccinated) and the flu/COVID-19 vaccine coadministration was more frequent in this group. A total of 51.0% HCWs were hesitant towards the coadministration, while residents and nurses showed the highest propensity to receive it. Conclusions: in the second year of the COVID-19 pandemic, the Fondazione’s influenza VCR continued to increase, with the greatest participation among HCWs aged 18–39 years. A potential propelling role of the COVID-19 vaccine coadministration was highlighted.

A Pilot Study of the Efficacy and Economical Sustainability of Acute Coronavirus Disease 2019 Patient Management in an Outpatient Setting.

ObjectiveTo report a preliminary experience of outpatient management of patients with Coronavirus disease 2019 (COVID-19) through an innovative approach of healthcare delivery.Patients and MethodsPatients evaluated at the Mild-to-Moderate COVID-19 Outpatient clinics (MMCOs) of San Raffaele University Hospital and Luigi Sacco University Hospital in Milan, Italy, from 1 October 2020 to 31 October 2021 were included. Patients were referred by general practitioners (GPs), Emergency Department (ED) physicians or hospital specialists (HS) in case of moderate COVID-19. A classification and regression tree (CART) model predicting ED referral by MMCO physicians was developed to aid GPs identify those deserving immediate ED admission. Cost-effectiveness analysis was also performed.ResultsA total of 660 patients were included. The majority (70%) was referred by GPs, 21% by the ED and 9% by HS. Patients referred by GPs had more severe disease as assessed by peripheral oxygen saturation (SpO2), ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), C-reactive protein (CRP) levels and interstitial involvement at lung ultrasound. Among them, 18% were addressed to the ED following MMCO assessment. CART analysis identified three independent predictors, namely home-measured SpO2, age and body mass index (BMI), that robustly divide patients into risk groups of COVID-19 severity. Home-measured SpO2 < 95% and BMI ≥ 33 Kg/m2 defined the high-risk group. The model yielded an accuracy (95% CI) of 83 (77–88)%. Outpatient management of COVID-19 patients allowed the national healthcare system to spare 1,490,422.05 € when compared with inpatient care.ConclusionMild-to-moderate COVID-19 outpatient clinics were effective and sustainable in managing COVID-19 patients and allowed to alleviate pressure on EDs and hospital wards, favoring effort redirection toward non-COVID-19 patients.

Unconventional CD147‐dependent platelet activation elicited by SARS‐CoV‐2 in COVID‐19

BackgroundPlatelet activation and thrombotic events characterizes COVID‐19. ObjectivesTo characterize platelet activation and determine if SARS‐CoV‐2 induces platelet activation. Patients/MethodsWe investigated platelet activation in 119 COVID‐19 patients at admission in a university hospital in Milan, Italy, between March 18 and May 5, 2020. Sixty‐nine subjects (36 healthy donors, 26 patients with coronary artery disease, coronary artery disease, and seven patients with sepsis) served as controls. ResultsCOVID‐19 patients had activated platelets, as assessed by the expression and distribution of HMGB1 and von Willebrand factor, and by the accumulation of platelet‐derived (plt) extracellular vesicles (EVs) and HMGB1+ plt‐EVs in the plasma. P‐selectin upregulation was not detectable on the platelet surface in a fraction of patients (55%) and the concentration of soluble P‐selectin in the plasma was conversely increased. The plasma concentration of HMGB1+ plt‐EVs of patients at hospital admission remained in a multivariate analysis an independent predictor of the clinical outcome, as assessed using a 6‐point ordinal scale (from 1 = discharged to 6 = death). Platelets interacting in vitro with SARS‐CoV‐2 underwent activation, which was replicated using SARS‐CoV‐2 pseudo‐viral particles and purified recombinant SARS‐CoV‐2 spike protein S1 subunits. Human platelets express CD147, a putative coreceptor for SARS‐CoV‐2, and Spike‐dependent platelet activation, aggregation and granule release, release of soluble P‐selectin and HMGB1+ plt‐EVs abated in the presence of anti‐CD147 antibodies. ConclusionsHence, an early and intense platelet activation, which is reproduced by stimulating platelets in vitro with SARS‐CoV‐2, characterizes COVID‐19 and could contribute to the inflammatory and hemostatic manifestations of the disease.

Comparison of different sets of immunological tests to identify treatable immunodeficiencies in adult bronchiectasis patients.

BackgroundThe reported prevalence of immunodeficiencies in bronchiectasis patients is variable depending on the frequency and extent of immunological tests performed. European Respiratory Society guidelines recommend a minimum bundle of tests. Broadening the spectrum of immunological tests could increase the number of patients diagnosed with an immunodeficiency and those who could receive specific therapy. The primary objective of the present study was to assess the performance of different sets of immunological tests in diagnosing any, primary, secondary or treatable immunodeficiencies in adults with bronchiectasis.MethodsAn observational, cross-sectional study was conducted at the Bronchiectasis Program of the Policlinico University Hospital in Milan, Italy, from September 2016 to June 2019. Adult outpatients with a clinical and radiological diagnosis of bronchiectasis underwent the same immunological screening during the first visit when clinically stable consisting of: complete blood count; immunoglobulin (Ig) subclass tests for IgA, IgG, IgM and IgG; total IgE; lymphocyte subsets; and HIV antibodies. The primary endpoint was the prevalence of patients with any immunodeficiencies using five different sets of immunological tests.ResultsA total of 401 bronchiectasis patients underwent the immunological screening. A significantly different prevalence of bronchiectasis patients diagnosed with any, primary or secondary immunodeficiencies was found across different bundles. 44.6% of bronchiectasis patients had a diagnosis of immunodeficiency when IgG subclasses and lymphocyte subsets were added to the minimum bundle suggested by the guidelines.ConclusionA four-fold increase in the diagnosis of immunodeficiencies can be found in adults with bronchiectasis when IgG subclasses and lymphocyte subsets are added to the bundle of tests recommended by guidelines.

After Action Reviews to assess COVID-19 hospital responses

IntroductionAfter-Action Reviews (AARs) are healthcare management tools applied to evaluate responses to public health emergencies, identifying best practices and challenges. They are included in the International Health Regulations (IHR) and recommended by the World Health Organization (WHO). The aim of this study was to adapt the WHO AAR guidelines to assess the response during the COVID-19 first epidemic wave (February 22nd-May 3rd, 2020) at San Raffaele Scientific Institute, a large university hospital in Milan, Italy. The hospital treated 951 patients and underwent massive re-organization.MethodsWe developed a hospital-oriented AAR based on the key-informant interview format. After establishing an AAR planning and analysis team, an ad-hoc questionnaire was designed to explore four areas: i)Staff management; ii)Logistics and supplies; iii)Diagnosis and clinical management; iv)Communication. The questionnaire was used to support 36 semi-structured interviews of professionals with executive, clinical, technical and administrative roles within the hospital.ResultsThe hospital response was rated as overall effective and sufficiently prompt. Participants stressed the key roles played by: i)strong governance and coordination; ii)readiness and availability of healthcare personnel; iii)multidisciplinary model of care based on levels of intensity. Major challenges concerned communication strategies and staff training. In addition, participants highlighted the need for greater collaboration among hospitals and primary care services.ConclusionsThis study represents one of the first applications of an AAR to the COVID-19 emergency and to the hospital setting. The tool provided San Raffaele's hospital management with a multi-layered analysis of the emergency response that informed the critical planning for next phases of the pandemic response. The tool can be adapted to other settings to pursue continuous operational improvement.Key messages After-action reviews are healthcare managements tools used to to evaluate a country or government’s response to infectious disease outbreaks, environmental or natural disasters and societal crises.After Action Reviews can be adapted or scaled for other settings to pursue continuous operational improvement and support preparedness strategies for future public health emergencies.

Nasopharyngeal Testing among Healthcare Workers (HCWs) of a Large University Hospital in Milan, Italy during Two Epidemic Waves of COVID-19.

Background: since October 2020, a second SARS-CoV-2 epidemic wave has hit Italy. We investigate the frequency of positive nasopharyngeal swabs among HCWs during the two waves and the association with occupation and demographic characteristics. Methods: this is a retrospective, observational study conducted in a large university hospital in Milan, Northern Italy. We defined two epidemic waves: 1st (February 2020–July 2020) and 2nd (August 2020–January 2021). Occupational and demographic characteristics of HCWs who underwent nasopharyngeal swabs for SARS-CoV-2 were collected. Results: in the 1st wave, 242 positive subjects (7.2%) were found among 3378 HCWs, whereas in the 2nd wave, the positive subjects were 545 out of 4465 (12.2%). In both epidemic waves positive NPSs were more frequent among HCWs with health-related tasks and lower among students (p < 0.001). However, in the 2nd wave, workers engaged in non-health-related tasks had a peak of 20.7% positivity. Among 160 positive HCWs in the 1st wave who were tested again in the 2nd wave, the rate of reinfection based on SARS-CoV2 RNA cycle quantification value was 0.6%. Conclusions: during the 2nd epidemic wave, we confirmed a significant impact of COVID-19 among HCWs. The rise of infection rate among HCWs seems to reflect the increasing spread of SARS-CoV-2 among the overall population.