High-resolution methylome analysis uncovers stress-responsive genomic hotspots and drought-sensitive transposable element superfamilies in the clonal Lombardy poplar.

DNA methylation is environment-sensitive and can mediate stress responses. In trees, changes in the environment might cumulatively shape the methylome landscape over time. However, because high-resolution methylome studies usually focus on single environmental cues, the stress-specificity and long-term stability of methylation responses remain unclear. Here, we studied the methylome plasticity of a Populus nigra cv. 'Italica' clone widely distributed across Europe. Adult trees from different geographic locations were clonally propagated in a common garden experiment and exposed to cold, heat, drought, herbivory, rust infection, and salicylic acid treatments. Whole-genome bisulfite sequencing revealed stress-induced and naturally occurring DNA methylation variants. In CG/CHG contexts, the same genomic regions were often affected by multiple stresses, suggesting a generic methylome response. Moreover, these variants showed striking overlap with naturally occurring methylation variants between trees from different locations. Drought treatment triggered CHH hypermethylation of transposable elements, affecting entire superfamilies near drought-responsive genes. Thus, we revealed genomic hotspots of methylation change that are not stress-specific and that contribute to natural DNA methylation variation, and identified stress-specific hypermethylation of entire transposon superfamilies with possible functional consequences. Our results underscore the importance of studying multiple stressors in a single experiment for recognizing general versus stress-specific methylome responses.

Diversity, integration, and variability of intergenerational relationships in old age: New insights from personal network research.

Relationships between family members from different generations have long been described as a source of solidarity and support in aging populations and, more recently, as a potential risk factor for COVID-19 contagion. Personal or egocentric network research offers a powerful kit of conceptual and methodological tools to study these relationships, but this has not yet been employed to its full potential in the literature. We investigate the heterogeneity, social integration, and individual correlates of intergenerational relationships in old age analyzing highly granular data on the personal networks of 230 older adults (2747 social ties) from a local survey in one of the areas of the world at the forefront of global aging trends (northern Italy). Using information on different layers in broad egocentric networks and on the structure of connectivity among the social contacts of aging people, we propose multiple conceptualizations and measures of intergenerational connectedness. Results show that intergenerational relationships are strongly integrated, but also highly diverse and variable, in older adults' social networks. Different types of intergenerational ties exist in different network layers, with various relational roles, degrees of tie strength, and patterns of association with individual and tie characteristics. We discuss how new and existing personal network data can be leveraged to consider novel questions and hypotheses about intergenerational relationships in contemporary aging families.

The contribution of the private healthcare sector during the COVID-19 pandemic: the experience of the Lombardy Region in Northern Italy.

Introduction: In Lombardy, the first European region hit by the COVID-19 pandemic, for decades the regional public healthcare service has followed a mixed delivery model with extensive involvement of private accredited providers. The study aimed at examining the role of the private sector in delivering healthcare services (diagnosis, hospitalization, and vaccination) during the pandemic. Study design: Healthcare system study. Methods: We analysed regional healthcare data referring to the period from March 2020 onwards to assess the availability of acute care and intensive care hospital beds, SARS-CoV-2 tests, and COVID-19 vaccinations. We specifically examined healthcare offered by private accredited providers within the region. Results: Of the 12,306 converted beds for COVID-19 treatment, 4,975 (40%) were in accredited private hospitals. Intensive care beds increased by 95%, reaching 1,755, with 484 (28%) in accredited private hospitals. Since the pandemic onset, 28.9 million (62%) of SARS-CoV-2 tests were conducted by private accredited facilities including pharmacies. Private sector actively contributed to the COVID-19 vaccination campaign administering over 2.6 million doses in 2021, enhancing vaccination capacity to its peak. Conclusions: The longstanding relationship between the public and private sectors within the Lombardy regional healthcare service facilitated a rapid increase in hospital bed capacity, the upscaling of SARS-CoV-2 testing capacity, and the achievement of vaccination goals to address the COVID-19 emergency. Therefore, alongside a robust and adequately funded public healthcare service, the private sector serves as an asset to enhance the resilience of healthcare systems, in line with WHO indications.

Proximal hip fractures in 71,920 elderly patients: incidence, epidemiology, mortality and costs from a retrospective observational study.

BACKGROUND: The risk of proximal femoral fractures increases with aging, causing significant morbidity, disability, mortality and socioeconomic pressure. The aims of the present work are (1) to investigate the epidemiology and incidence of these fractures among the elderly in the Region of Lombardy; (2) to identify the factors influencing survival; (3) to identify the factors influencing hospitalization and post-operative costs. METHODS: The Region of Lombardy provided anonymized datasets on hospitalized patients with a femoral neck fracture between 2011 and 2016, and anonymized datasets on extra-hospital treatments to track the patient history between 2008 and 2019. Statistical evaluations included descriptive statistics, survival analysis, Cox regression and multiple linear models. RESULTS: 71,920 older adults suffered a femoral fracture in Lombardy between 2011 and 2016. 76.3% of patients were females and the median age was 84. The raw incidence of fractures was stable from year 2011 to year 2016, while the age-adjusted incidence diminished. Pertrochanteric fractures were more spread than transcervical fractures. In patients treated with surgery, receiving treatment within 48 h reduced the hazard of death within the next 24 months. Combined surgical procedures led to increased hazard in comparison with arthroplasty alone, while no differences were observed between different arthroplasties and reduction or fixation. In patients treated conservatively, age and male gender were associated with higher hazard of death. All patients considered, the type of surgery was the main factor determining primary hospitalization costs. A higher number of surgeries performed by the index hospital in the previous year was associated with financial savings. The early intervention significantly correlated with minor costs. CONCLUSIONS: The number of proximal femoral fractures is increasing even if the age-adjusted incidence is decreasing. This is possibly due to prevention policies focused on the oldest cohort of the population. Two policies proved to be significantly beneficial in clinical and financial terms: the centralization of patients in high-volume hospitals and a time limit of 48 h from fracture to surgery. TRIAL REGISTRATION: Non applicable.

Impact of the post-COVID-19 condition on health care after the first disease wave in Lombardy.

BACKGROUND: Lombardy was affected in the early months of 2020 by the SARS-CoV-2 pandemic with very high morbidity and mortality. The post-COVID-19 condition and related public health burden are scarcely known. SETTING AND DESIGN: Using the regional population administrative database including all the 48,932 individuals who survived COVID-19 and became polymerase-chain-reaction negative for SARS-CoV-2 by 31 May 2020, incident mortality, rehospitalizations, attendances to hospital emergency room, and outpatient medical visits were evaluated over a mid-term period of 6 months in 20,521 individuals managed at home, 26,016 hospitalized in medical wards, and 1611 in intensive care units (ICUs). These data were also evaluated in the corresponding period of 2019, when the region was not yet affected by the pandemic. Other indicators and proxies of the health-care burden related to the post-COVID condition were also evaluated. MAIN RESULTS: In individuals previously admitted to the ICU and medical wards, rehospitalizations, attendances to hospital emergency rooms, and out-patient medical visits were much more frequent in the 6-month period after SARS-CoV-2 negativization than in the same prepandemic period. Performances of spirometry increased more than 50-fold, chest CT scans 32-fold in ICU-admitted cases and 5.5-fold in non-ICU cases, and electrocardiography 5.6-fold in ICU cases and twofold in non-ICU cases. Use of drugs and biochemical tests increased in all cases. CONCLUSIONS: These results provide a real-life picture of the post-COVID condition and of its effects on the increased consumption of health-care resources, considered proxies of comorbidities.

A snapshot of emergency neurology management in the Lombardy Region, Italy.

BACKGROUND: The assessment of human and diagnostic resources is a prerequisite to improving the management of emergency neurology. OBJECTIVE: To provide a landscape on the organization of the Lombardy Region hospitals for emergency neurological care management. METHODS: We designed an anonymized questionnaire including 6 sections with 21 questions on facilities, human and diagnostic resources, and intra- and between-hospital connections. The time needed to fill the questionnaire was estimated not to exceed 6 min. RESULTS: The questionnaire was returned by 33/41 (80.5%) hospitals, 22 classified as level 1 (spoke), and 11 as level 2 (hub). Five of 33 (15%) did not have a neurology unit. The mean annual rate of neurological consultations accounted for 5-6% of all admissions (range 2-8%) and did not differ between levels 1 and 2 hospitals. Neurologists were 24-h available in 21/33 (64%) hospitals, 12-h and on call at night in 6 (18%), less than 12 h without nocturnal availability in 5 (15%), and neither present nor available in 1 (3%). Brain CT and CSF examinations were 24-h universally available, whereas EEG and neurosonology were not in most hospitals. Despite angio-CT was 24-h available in more than 75% of the hospitals, only 45% of them had 24-h availability of diffusion/perfusion imaging, and 43% were not available at any time. Only 12% of the hospitals had 24-h availability of neuroradiologists and 6% of interventional neuroradiologists. CONCLUSION: Our data, while emphasizing current critical issues, offer clues for identifying priorities and improving the management of emergency and time-dependent neurological diseases.

Vascular Surgery During COVID-19 Emergency in Hub Hospitals of Lombardy: Experience on 305 Patients.

OBJECTIVE: During the most aggressive phase of the COVID-19 outbreak in Italy, the Regional Authority of Lombardy identified a number of hospitals, named Hubs, chosen to serve the whole region for highly specialised cases, including vascular surgery. This study reports the experience of the four Hubs for Vascular Surgery in Lombardy and provides a comparison of in hospital mortality and major adverse events (MAEs) according to COVID-19 testing. METHODS: Data from all patients who were referred to the Vascular Surgery Department of Hubs from 9 March to 28 April 2020 were collected prospectively and analysed. A positive COVID-19 polymerase chain reaction swab test, or symptoms (fever > 37.5 °C, upper respiratory tract symptoms, chest pain, and contact/travel history) associated with interstitial pneumonia on chest computed tomography scan were considered diagnostic of COVID-19 disease. Patient characteristics, operative variables, and in hospital outcomes were compared according to COVID-19 testing. A multivariable model was used to identify independent predictors of in hospital death and MAEs. RESULTS: Among 305 included patients, 64 (21%) tested positive for COVID-19 (COVID group) and 241 (79%) did not (non-COVID group). COVID patients presented more frequently with acute limb ischaemia than non-COVID patients (64% vs. 23%; p < .001) and had a significantly higher in hospital mortality (25% vs. 6%; p < .001). Clinical success, MAEs, re-interventions, and pulmonary and renal complications were significantly worse in COVID patients. Independent risk factors for in hospital death were COVID (OR 4.1), medical treatment (OR 7.2), and emergency setting (OR 13.6). COVID (OR 3.4), obesity class V (OR 13.5), and emergency setting (OR 4.0) were independent risk factors for development of MAEs. CONCLUSION: During the COVID-19 pandemic in Lombardy, acute limb ischaemia was the most frequent vascular disease requiring surgical treatment. COVID-19 was associated with a fourfold increased risk of death and a threefold increased risk of major adverse events.

The Lombardy Emergency Medical System Faced with COVID-19: The Impact of Out-of-Hospital Outbreak.

OBJECTIVE: The Lombardy region was among the areas most affected by COVID-19 infection worldwide; the Lombardy Emergency Medical System (EMS) responded immediately to this emergency. We analyzed several critical aspects to understand what occurred in that region. METHODS: This retrospective study compares the events managed by the dispatch center and the characteristics of the patients transported to the hospital -age, sex, SpO2, deaths- managed by the EMS in Brescia and Bergamo provinces between March-April 2020 and March-April 2019. Ambulances' waiting time at the hospitals before discharging patients and the patients' severity at emergency department admission were also analyzed. RESULTS: EMS managed 37,340 events in March-April 2020, +51.5% versus 2019. "Breathing" or "Infective" events reported to the dispatch center increased more than ten-fold (OR 25.1, p < 0.0001) in March 2020 and two-fold in April 2020 compared to 2019 (OR 3, p < 0.0001). Deaths increased +246% (OR 1.7, p < 0.0001), and patients not transported to hospital +481% (OR 2.9, p < 0.0001) in March 2020 compared to 2019. In some hospitals, ambulances waited more than one hour before discharging the patients, and the emergency departments doubled the admission of critically ill patients. Transported patients for "Breathing" or "Infective" events were primarily males (OR 1.5, p < 0.0001). The patients had lower SpO2 in 2020 than in 2019 and they were younger. CONCLUSIONS: The Lombardy region experienced an unexpected outbreak in an extremely short timeframe and in a limited area. The EMS coped with this pandemic, covering an extremely higher number of requests, with a ten-fold increase in the number of events managed.

Comparison of ammonia air concentration before and during the spread of COVID-19 in Lombardy (Italy) using ground-based and satellite data.

Several anthropogenic activities have undergone major changes following the spread of the COVID-19 pandemic, which in turn has had consequences on the environment. The effect on air pollution has been studied in detail in the literature, although some pollutants, such as ammonia (NH3), have received comparatively less attention to date. Focusing on the case of Lombardy in Northern Italy, this study aimed to evaluate changes in NH3 atmospheric concentration on a temporal scale (the years from 2013 to 2019 compared to 2020) and on a spatial scale (countryside, city, and mountain areas). For this purpose, ground-based (from public air quality control units scattered throughout the region) and satellite observations (from IASI sensors on board MetOp-A and MetOp-B) were collected and analyzed. For ground-based measurements, a marked spatial variability is observed between the different areas while, as regards the comparison between periods, statistically significant differences were observed only for the countryside areas (+31% in 2020 compared to previous years). The satellite data show similar patterns but do not present statistically significant differences neither between different areas, nor between the two periods. In general, there have been no reduction effects of atmospheric NH3 as a consequence of COVID-19. This calls into question the role of the agricultural sector, which is known to be the largest responsible for NH3 emissions. Even if the direct comparison between the two datasets shows little correlation, their contextual consideration allows making more robust considerations regarding air pollutants.

Is administered competition suitable for dealing with a public health emergency? Lessons from the local healthcare system at the centre of early COVID-19 outbreak in Italy.

OBJECTIVES: The Lombardy Region, Italy, was the most severely affected by the COVID-19 outbreak. In absence of effective treatments and with basic hygiene measures made mandatory, Lombardy response to COVID-19 relied on its healthcare system characteristics, the administered competition or "quasi-market" model. The aim of the study was to review the strengths and weaknesses of Lombardy's response during the first wave of the COVID-19 epidemic, to explore whether the healthcare model influenced crisis management and describe which policies could help to contain future outbreaks. The results are expected to provide similar healthcare systems with lessons to avoid mistakes and learn from best practice. METHODS: Data for quantitative analyses on the performance of the Lombardy and Veneto Regions healthcare systems were derived from existing government sources including the Italian Civil Protection Agency and the Ministry of Health. RESULTS: Lombardian quasi-market model, traditionally characterized by a strong hospital network, was held responsible for many suboptimal outcomes. According to critics, years of disinvestments in community care resulted in a hospital overload. However, the same model was responsible for other positive outcomes which have been substantially neglected, such as the opportunity to test for effective containment treatments in a safe environment and rapidly extend the number of beds. CONCLUSIONS: The performance of a quasi-market model against public health emergencies largely depends on integration between policy-makers and balance between healthcare providers, which require clear regulation. Reducing institutional fragmentation between levels of governance, improving the coordination of healthcare facilities and adopting telemedicine technologies are means by which healthcare networks could strengthen their resilience against future outbreaks.