Revolutionizing Blood Collection: Innovations, Applications, and the Potential of Microsampling Technologies for Monitoring Metabolites and Lipids.

Blood serves as the primary global biological matrix for health surveillance, disease diagnosis, and response to drug treatment, holding significant promise for personalized medicine. The diverse array of lipids and metabolites in the blood provides a snapshot of both physiological and pathological processes, with many routinely monitored during conventional wellness checks. The conventional method involves intravenous blood collection, extracting a few milliliters via venipuncture, a technique limited to clinical settings due to its dependence on trained personnel. Microsampling methods have evolved to be less invasive (collecting ≤150 µL of capillary blood), user-friendly (enabling self-collection), and suitable for remote collection in longitudinal studies. Dried blood spot (DBS), a pioneering microsampling technique, dominates clinical and research domains. Recent advancements in device technology address critical limitations of classical DBS, specifically variations in hematocrit and volume. This review presents a comprehensive overview of state-of-the-art microsampling devices, emphasizing their applications and potential for monitoring metabolites and lipids in blood. The scope extends to diverse areas, encompassing population studies, nutritional investigations, drug discovery, sports medicine, and multi-omics research.

Towards the Definition of the Molecular Hallmarks of Idiopathic Membranous Nephropathy in Serum Proteome: A DIA-PASEF Approach.

Idiopathic membranous nephropathy (IMN) is a pathologically defined disorder of the glomerulus, primarily responsible for nephrotic syndromes (NS) in nondiabetic adults. The underlying molecular mechanisms are still not completely clarified. To explore possible molecular and functional signatures, an optimised mass spectrometry (MS) method based on next-generation data-independent acquisition combined with ion-mobility was applied to serum of patients affected by IMN (n = 15) or by other glomerulopathies (PN) (n = 15). The statistical comparison highlighted a panel of 57 de-regulated proteins with a significant increase in lipoprotein-related proteins (APOC1, APOB, APOA1, APOL1 and LCAT) and a substantial quantitative alteration of key serpins (including A4, D1, A7, A6, F2, F1 and 1) possibly associated with IMN or NS and podocyte stress. A critical dysregulation in metabolisms of lipids (e.g., VLDL assembly and clearance) likely to be related to known hyperlipidemia in IMN, along with involvement of non-classical complement pathways and a putative enrolment of ficolin-2 in sustaining the activation of the lectin-mediated complement system have been pinpointed. Moreover, mannose receptor CD206 (MRC1-down in IMN) and biotinidase (BTD-up in IMN) are able alone to accurately distinguish IMN vs. PN. To conclude, our work provides key proteomic insights into the IMN complexity, opening the way to an efficient stratification of MN patients.

Suture-Mediated Patent Foramen Ovale Closure Using the NobleStitch EL: Results from a Hospital-Based HTA.

(1) Background: Patent foramen ovale (PFO) is a congenital abnormality present in up to 25% of the general population, and it is a relevant cause of cryptogenic stroke. We applied the hospital-based HTA model (AdHopHTA) to conduct a multidimensional assessment of NobleStitch EL, an innovative suture-mediated PFO closure device. We compared it to Amplatzer PFO Occluder (APO) to provide evidence to inform technologies' governance in hospital settings. (2) Methods: For each AdHopHTA dimension we: systematically retrieved available evidence from the literature applying the PRISMA guidelines and then analyzed original clinical and cost data of a NobleStitch EL device at San Raffaele research hospital in Milan (Italy). The economic dimension was analyzed through activity-based costing and a cost analysis. We conducted semi-structured interviews with selected healthcare professionals to explore the organizational, legal, social, and ethical impact. (3) Results: A single study was included for the NobleStitch EL, with 10 for APO. Both literature data and original data showed comparable safety. Efficacy data analysis found that the PFO closure was at 89% for NobleStitch EL vs. 89-97% for APO. APO has a better impact on the budget and minor process costs. Consulted experts reported that the organizational impact of NobleStitch EL in the short and the long run as null, albeit a better impact under the social and the ethical aspects. (4) Conclusion: We suggest that there is inadequate evidence to conclude the relative efficacy of NobleStitch EL as compared to APO. Nevertheless, this report shows a good safety profile and higher costs for NobleStitch EL, with no organizational or legal impact. Further studies in selected population are recommended.

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

Objective: To report a preliminary experience of outpatient management of patients with Coronavirus disease 2019 (COVID-19) through an innovative approach of healthcare delivery. Patients and Methods: Patients 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. Results: A 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. Conclusion: Mild-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.

Efficacy and safety of Impella 5.0 in cardiogenic shock: an updated systematic review.

Aim: The impact on safety and efficacy outcomes of Impella 5.0 in cardiogenic shock (CS) has not been systematically assessed. Materials & methods: We conducted a systematic review of the literature (PROSPERO protocol: CRD42020164680) to critically appraise available evidence on Impella 5.0 comparative safety, efficacy and effectiveness. Results: Of 244 retrieved citations, 17 original articles met the a priori defined inclusion criteria. All included studies had a retrospective study design and, overall, reported on, respectively, 52 and 67 different safety and efficacy/effectiveness outcomes. Thirty-day survival rates ranged from 40 to 94%, myocardial recovery from 18 to 93%. Conclusion: Impella 5.0 provides a full cardiac support, it is associated with a lower rate of vascular complications, it represents a valuable bridge-to-decision and allows for resolution of intercurrent clinical conditions. As available data suggest Impella 5.0 good performance in CS of various etiologies, more solid evidence will come from much-needed large-scale all-comer registries and prospective multicenter randomized trials.

Cardiogenic shock (CS) is a life-threatening condition in which the heart cannot pump enough blood to meet the body's needs. Despite advances in biomedical research and technology, CS is still associated with high mortality. Some devices (Intra-aortic balloon pump (IABP), Impella, Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO), placed through vascular accesses, can support the heart in the failing phase. The aim of this systematic review of the scientific literature is to evaluate safety, efficacy and effectiveness of Impella 5.0 in CS.

Physician-to-Nurse Handover: A Systematic Review on the Effectiveness of Different Models.

OBJECTIVES: Effective professional communication and accurate transfer of relevant clinical information are crucial components of healthcare delivery. National and international health authorities strongly recommend the adoption of effective handover practice. Still, scant evidence is available on the impact of different multiprofessional handover models. METHODS: We carried out a systematic review following the Prepared Items for Systematic Reviews and Meta-Analysis guidelines to retrieve, pool, and critically appraise the available evidence on the effectiveness of different physician-to-nurse handover models adopted in inpatient settings. RESULTS: We identified 1.243 citations searching the databases Medline, Embase, and CINAHL. After screening, 10 studies were included in the review reporting results on the effectiveness of 8 different handover models, measured on 44 different outcomes, grouped into: (1) process of care and efficiency outcomes, (2) patients' outcomes, and (3) healthcare professionals-related outcomes. Overall, applying structured handover tools improve healthcare practice and selected outcomes; however, not only solid evidence on the effectiveness of different handover models is scant but also global consensus is lacking on which standardized measures and indicators to use to assess their impact. CONCLUSIONS: In times of healthcare delivery models of growing complexity, multiprofessional handover is a key component of care paths. Although there is overall consensus on the need for improving the quality and safety of multiprofessional handover, the evidence on the tools available to achieve it and the metrics to measure their impact is heterogeneous. We urge that rigorous studies are conducted to inform the planning, implementation, and monitoring of effective handover, with the ultimate aim of improving quality of care and patient safety.

COVID-19 second wave: appropriateness of admissions to the Emergency Department of a main metropolitan hospital in Milan.

BACKGROUND: In Europe, Italy and Lombardy, in autumn 2020, there was a steep increase in reported cases due to the second epidemic wave of SARS-Cov-2 infection. We aimed to evaluate the appropriateness of COVID-19 patients' admissions to the ED of the San Raffaele Hospital. METHODS: We compared data between the inter-wave period (IWP, from 1st to 30th September) and the second wave period (WP, 1st October to 15th November) focusing on the ED presentation, discharge priority colour code and outcomes. RESULTS: Out of 977 admissions with a SARS-Cov-2 positive swab, 6% were in the IWP and 94% in the WP. Red, yellow and white code increased (these latter from 1.8% to 5.4%) as well as self-presented in yellow and white code. Discharges home increased from 1.8% to 5.4%, while hospitalizations decreased from 63% to 51%. DISCUSSION: We found a rise in white codes (among self-presented patients), indicating inappropriateness of admissions. The increase in discharges suggests that several patients did not require hospitalization. CONCLUSIONS: The pandemic brought out the fundamental role of primary care to manage patients with low-intensity needs. The important increase in ED admissions of COVID-19 patients caused a reduction of NO-COVID-19 patients, with possible inadequate treatment.

After Action Reviews of COVID-19 response: Case study of a large tertiary care hospital in Italy.

BACKGROUND: After-Action Reviews (AARs) are management tools used to evaluate the response to public health emergencies at the national and subnational level. Aim of this study is to apply available AAR models to assess and critically appraise COVID-19 response of San Raffaele Scientific Institute, a large university hospital in Milan, Italy. METHODS: We designed an AAR based on the key-informant interview format, following the methodology proposed by the 2019 World Health Organization Guidance for AAR. After systematic assessment of the hospital reorganization, we conducted 36 semi-structured interviews to professionals with executive, clinical, technical and administrative roles. We designed an ad-hoc questionnaire exploring four areas: (i) staff management; (ii) logistics and supplies; (iii) COVID-19 diagnosis and clinical management; (iv) communication. RESULTS: Overall, the hospital response was evaluated as effective and sufficiently prompt. Participants stressed the relevance of: (i) strong governance and coordination; (ii) readiness and availability of healthcare personnel; (iii) definition of a model of care based on a multidisciplinary approach. Challenges were reported for communication management and staff training. CONCLUSIONS: This study is one of the first applications of the AAR to the COVID-19 response in hospital settings, which can be successfully adapted or scaled up to other settings in order to implement preparedness strategies for future public health emergencies.

How to get away with COVID-19: endoscopy during post-peak pandemic. A perspective review.

The SARS-CoV-2 pandemic has changed the way we work, and health care services have to adapt. The use of personal protective equipment (PPE) and the delay of non-urgent procedures were the immediate measures adopted by Gastrointestinal (GI) Endoscopy Units at the time of crisis. As the peak has now passed in most countries, GI facilities are facing the next challenge of this pandemic: service providers must adapt their routine work to a 'new normal'. Routine casework must resume, and waiting lists must be addressed: all in the awareness of the ongoing potential risks of COVID-19, and the threat of a second wave. In this review, we discuss strategies to manage the workload by improving procedure appropriateness and prioritization, whilst maintaining a 'COVID-free' environment. This includes monitoring of an adequate stock of PPE and the implications for the staff's workload, and the GI trainees' need of training.

COVID-19 mortality rate in nine high-income metropolitan regions.

We analyzed the spread of the COVID-19 epidemic in 9 metropolitan regions of the world with similar socio-demographic characteristics, daytime commuting population and business activities: the New York State, Bruxelles-Capital, the Community of Madrid, Catalonia, the Île-de-France Region, the Greater London county, Stockholms län, Hovedstaden (Copenhagen) and the Lombardy Region. The Lombardy region reported the highest COVID-19 crude mortality rate (141.0 x 100,000) 70-days after the onset of the epidemic, followed by the Community of Madrid (132.8 x 100,000) New York State (120.7 x 100,000). The large variation in COVID-19 mortality and case-fatality rates for COVID-19 in different age strata suggested a more accurate analysis and interpretation of the epidemic dynamics after standardization of the rates by age. The share of elder populations (>70 years) over total population varies widely in the considered study settings, ranging from 6.9% in Catalonia to 17.0% in Lombardy. When taking age distribution into consideration the highest standardized mortality rate was observed in the State of New York (257.9 x 100,000); with figures in most of the European regions concentrated between 123.3 x 100,000 in Greater London and 177.7 x 100,000 in Bruxelles-Capital, lower in French and Danish regions. We also report and critical appraise, when available, COVID-19 mortality figures in capital cities, nursing homes, as well as excess mortality at country level. Our data raise awareness on the need for a more in-depth epidemiological analysis of the current COVID-19 public health emergency that further explores COVID-19 mortality determinants associated with health services delivery, community-level healthcare, testing approaches and characteristics of surveillance systems, including classification of COVID-19 deaths.

Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy.

BACKGROUND: National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited. METHODS: All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated. RESULTS: Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56-75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5-11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60-99), with median PaO2/FiO2 ratio, 267 (IQR 184-314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4-16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality. CONCLUSION: In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.

The spread of COVID-19 in six western metropolitan regions: a false myth on the excess of mortality in Lombardy and the defense of the city of Milan.

We analyzed the spread of the COVID-19 epidemic in 6 metropolitan regions with similar demographic characteristics, daytime commuting population and business activities: the New York metropolitan area, the Île-de-France region, the Greater London county, Bruxelles-Capital, the Community of Madrid and the Lombardy region. The highest mortality rates 30-days after the onset of the epidemic were recorded in New York (81.2 x 100,000) and Madrid (77.1 x 100,000). Lombardy mortality rate is below average (41.4 per 100,000), and it is the only situation in which the capital of the region (Milan) has not been heavily impacted by the epidemic wave. Our study analyzed the role played by containment measures and the positive contribution offered by the hospital care system. (www.actabiomedica.it).

[The IRCCS San Raffaele Hospital organizational model to assess the clinical documentation completeness and the appropriateness of hospitalization: the SVAD experience and the results of the three-year period 2018-2020.] / Modello di organizzazione dei controlli interni di completezza della documentazione clinica e di appropriatezza dei ricoveri all'IRCCS Ospedale San Raffaele: il Servizio Valutazione Appropriatezza della Documentazione clinica (SVAD) e i risultati del triennio 2018-2020.

According to the progressive increase in the number of medical records checked by the Agenzia di Tutela della Salute (ATS) of the Metropolitan City of Milan, the San Raffaele Hospital established a Unit supporting healthcare personnel in clinical documentation management. Therefore, in 2003 the Servizio Valutazione Appropriatezza della Documentazione clinica (SVAD), consisting of a nursing staff highly qualified in checking the appropriateness of clinical pathways, completeness and correctness of the clinical documentation and appropriate coding in the hospital discharge cards, was set up in the Health Directorate. Since 2018, the Service has seen an increase in resources, a re-organization and integration with the Operating Units. The aim of the article is to describe the introduction of a new organizational model and the results obtained, with reference to the quality self-control carried out for the ATS. In order to conduct a descriptive analysis of the trend, the sample data, required by the ATS in the three-year period 2018-2020, stratified by outcome and consequent percentage of reduction on the reimbursement of hospitalization, were considered. We observe an overall percentage increase in medical records without any reduction from 2018 to 2020, going from 84% to 94% (+ 10%); at the same time, there is a constant trend of medical records with complete curtailment between 2018 and 2019, while there is a reduction between 2019 and 2020, going from 4% to 2% (-2%). The positive results demonstrate the essential role of SVAD and consolidate an alternative career for nursing staff.

Risk Management in healthcare: results from a national-level survey and scientometric analysis in Italy.

Risk management in healthcare, intended as all processes employed to detect, monitor, assess, mitigate, and prevent risks in healthcare facilities and safeguard patient safety, is a crucial component of Italy' National Health Service. Aim of the current study is to assess the role and progress of  research and training, in the field of Risk Management. We carried out a scientometric analysis to quantify and describe scientific outputs on Risk Management at the global and national level, over the last forty years; in addiction, we conducted a national-level cross-sectional survey to systematically retrieve and assess research and training activities within Italian postgraduate medical programmes in Hygiene and Preventive Medicine.   We report increasing scientific production on Risk Management-related topics from 1980 to 2017 at the global level (12% annual increase rate). Clinical Trials and Systematic reviews/meta-analysis make up for respectively 5% and 6% of global scientific output. Italy ranks 4th for scientific production, after USA, UK and Germany. 88% of Italian postgraduate medical programmes in Hygiene and Preventive medicine research on Risk Management, 42% through international collaborations. The main research themes are Healthcare-Associated Infections (HAIs) (97%), analysis of organizational models for safety in healthcare (62%), while training is focused on internships (87%) and academic lectures (73%). While research provides the evidence required to plan, implement and monitor effective interventions in healthcare risk management, training allows its dissemination in a synergic action to promote the value of patient safety and quality of care.