Northern Italy Research Articles

All-cause, cardiovascular disease and cancer mortality in the population of a large Italian area contaminated by perfluoroalkyl and polyfluoroalkyl substances (1980–2018)

BackgroundPer- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018.MethodsThe Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20–84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater.ResultsDuring the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107–109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer.ConclusionsFor the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.

Long-term outcomes of the Italian Mycobacterium avium subspecies paratuberculosis control programme for dairy cattle.

The considerable epidemiological and economic implications of paratuberculosis, caused by Mycobacterium avium subspecies paratuberculosis (MAP), have placed importance on control efforts aimed at preventing MAP transmission. In this context, Italy issued national guidelines for the control and status certification of MAP in dairy cattle in 2013. We assessed the long-term outcomes of the Italian MAP control programme for 14 dairy farms located in northern Italy by retrospectively reviewing the results of yearly serological tests, presence of clinical cases, MAP faecal shedding in serologically positive animals, farm management and health ranking as indicators of herd health between 2014 and 2021. A significantly higher number of serologically positive animals were observed between 2014 and 2016 than between 2017 and 2021, as well as an improving trend in the paratuberculosis health ranking for nine of the 14 farms. No clinical cases were reported. MAP shedding was detected in 9.4% of serologically positive animals. Discarding colostrum and prioritised culling of seropositive animals assisted by adoption of standardised serological testing were presumed to have a key role in MAP control, despite the reluctance of some farmers to address hygienic issues and improve the separation of calves from adult animals. The small number of farms included in this study and the fact that these were not randomly selected may limit the generalisability of the findings. The Italian paratuberculosis control plan has provided measures to limit the uncontrolled spread of MAP infection within and between herds by promoting animal trading between farms certified as negative or low risk.

Production technique and multi-analytical characterization of a paint-plastered ceiling from the Late Antique villa of Negrar (Verona, Italy)

The research focuses on analyzing the production techniques and materials of a Roman paint-plastered ceiling from a Late Antique Roman villa near Negrar (Verona, Italy), recently uncovered. Stylistic features of the decoration, found in reworked collapse debris during the villa’s excavation, date the ceiling to the original construction phase in the 4th century CE. The paper presents the protocol we adopted for recovering and analyzing the painted decoration of the villa, which was in-laboratory recomposed in its original layout after a meticulous and systematic retrieval of fragmented materials. Microsamples of mortar and pigment were then taken to fully reconstruct the execution technique and raw materials used in the paint-plastered ceiling, detailing the application of the tectorium and pigment preparation. Mortar samples were analyzed to define preparatory layer properties, using various analytical techniques including Transmitted-Light Polarized Optical Microscopy (TL-OM) and Scanning Electron Microscopy with Energy Dispersive X-Ray Analysis (SEM-EDS). Optical reflected-light microscopy detected guide incisions on the preparatory mortar, while Reflected-Light Optical Microscopy (RL-OM) revealed the microstratigraphy of pictorial micro-layers. Micro-samplings of painted decorations were conducted to define pigment palettes, determining their mineralogical composition through X-Ray Powder Diffraction (XRPD) analysis coupled with micro-Raman analyses for the determination of carbon-based compounds. The research aims to establish a comprehensive protocol for future endeavors, integrating archaeological reassembly with precise micro-analyses of pigments and mortars, deciphering the intricate layout of ancient, fragmented decorations. This study is the first of its kind in Northern Italy, overcoming challenges posed by fragmented and reworked artifacts in previous research, enabling detailed analytical studies like those conducted here. Moreover, this study of the paint-plastered ceiling of the Late Roman villa of Negrar aims to provide a new impulse for the knowledge of Late Antique painting techniques and materials, which were only marginally considered within Roman painting tradition so far.

Estimating risk to prevent damage: predicting and preventing coypu (Myocastor coypus) damage to transport infrastructure.

A major impact of invasive Myocastor coypus in their introduction range is the collapse of riverbanks and nearby infrastructure, such as railway lines, due to the species' burrowing activities. Because widespread implementation of preventive measures along watercourses is unfeasible, identifying susceptible areas is key to guide targeted management actions. This study used species-habitat models to: (i) identify local environmental features of the railway line/watercourse intersections (RLWIs) that make them particularly susceptible to coypu damage, and (ii) predict species occurrence probability over a wide lowland-hilly area of northern Italy (Lombardy) to identify priority areas for monitoring. Local-scale models identified that the RLWIs most susceptible to burrowing were those surrounded by arable land with interspersed hedgerows locally characterized by high herbaceous vegetation and clay soil. In urbanized areas and areas of intensive agriculture, coypu dens were generally located significantly closer to the railway, increasing the risk of collapse. A landscape-scale species distribution model showed that lowland areas along major rivers and lake shores, and also agricultural areas with a dense minor hydrographic network, particularly in the southeast of the study area, are more likely to be occupied by coypu. Local-scale models showed that specific environmental characteristics increase the risk of burrowing near RLWIs. The landscape-scale model allowed us to predict which areas require thorough monitoring of RLWIs to search for such local characteristics to implement preventive management measures. The proposed model-based framework can be applied to any geographical context to predict and prevent coypu damage. © 2024 Society of Chemical Industry.

Multicriteria-decision support for master plan scheduling: urban regeneration of an industrial area in Northern Italy

Urban regeneration programs involve a series of intricate activities that utilize human, material, and financial resources, executed at varying times and in diverse manners. Within this complex scenario, a major challenge lies in effectively managing concurrent developments across multiple buildings and infrastructure projects, while also harmonizing the interests of all parties engaged in urban regeneration initiatives. This paper introduces a multi-step strategy designed to enhance and streamline urban management amid the multifaceted decision-making processes characteristic of urban regeneration efforts. Specifically, the multi-criteria decision-making model ELECTRE TRI-B is employed to sort the array of basic tasks within a complex transformation endeavor into priority groups based on various evaluative criteria. To ascertain the significance of these criteria and rank each task according to the interests of the stakeholders likely to be impacted, a panel of specialists, including construction experts, economists, and environmental assessors, is convened. Following this, project actions are organized in a Gantt chart reflecting the construction priority determined by the evaluation model. This approach facilitated the temporal organization of master plan activities, incorporating insights from a broad spectrum of experts including municipal technical staff, professionals, and the community at large. The findings indicate that this comprehensive and interactive approach to performance measurement enabled the handling of extensive datasets and the refinement of financial, economic, environmental, and social resources, all while adhering to logical constraints and urban policy demands.

The impact of temperature on increased airborne pollen and earlier onset of the pollen season in Trentino, Northern Italy

The impact of climate change on ecosystems can be assessed through pollen dispersion data, which acts as a proxy for the plant flowering stage. The aim of this study is to verify if changes occurred in the season and concentration of airborne pollen in Trentino (Northern Italy), and to evaluate if temperature (T), precipitation (P), and/or land use influenced such changes in the period 1989–2018. Airborne pollen, sampled by a Hirst-type trap, was analyzed by light microscopy, and pollen concentrations were obtained. Twenty-four taxa, covering 95% of the local pollen spectrum, were considered for this study. A significant upward trend in annual pollen integral (APIn) is the main outcome over the study period. The increase in APIn is more evident when analyzing the data in three decadic blocks, both for all the considered taxa (+ 58%) and for Arboreal Pollen (AP; + 155%). Considering both the annual data and the decadic blocks, APIn shows a significant positive trend for Cupressaceae/Taxaceae, Ulmus, Populus, Salix, Ostrya, Quercus, Olea (AP), and Plantago, Cannabaceae, Ambrosia (non-arboreal pollen, NAP); a significantly earlier start of the Main Pollen Season (MPS) is proved for Rumex and Poaceae. APIn for 24 taxa shows a significant positive correlation with annual T min (< 0.005) and T mean (< 0.001), both of which showing a significant increase, and a negative correlation (< 0.025) with the number of frost days. From a human health perspective, higher temperatures, driven by climate changes, lead to higher concentrations of allergenic airborne pollen, turning into a higher risk for allergy sufferers.

Level of implementation of multimodal strategies for infection prevention and control interventions and prevalence of healthcare-associated infections in Northern Italy

BackgroundIn November 2022, Italy participated in the third edition of the European Centre for disease prevention and control (ECDC) point prevalence survey (PPS) of healthcare-associated infections (HAIs) in acute-care hospitals. A questionnaire based on the WHO infection prevention and control assessment framework (IPCAF) was included, which aims to investigate multimodal strategies for the implementation of IPC interventions.MethodsA PPS was conducted using the ECDC PPS protocol version 6.0. The Regional health authority of the region of Piedmont, in north-western Italy, chose to enlist all public acute-care hospitals. Data were collected within one day per each ward, within 3 weeks in each hospital, at hospital, ward and patient level. A score between 0–1 or 0–2 was assigned to each of the 9 items in the IPCAF questionnaire, with 14 points representing the best possible score. HAI prevalence was calculated at the hospital-level as the percentage of patients with at least one HAI over all included patients. Relations between HAI prevalence, IPCAF score, and other hospital-level variables were assessed using Spearman's Rho coefficient.ResultsIn total, 42 acute-care hospitals of the region of Piedmont were involved, with a total of 6865 included patients. All participant hospitals reported they employed multimodal strategies to implement IPC interventions. The median IPCAF overall score was 11/14 (interquartile range, IQR: 9.25–12). The multimodal strategy with the highest level of adherence was education and training, followed by communication and reminders. Strategies with the lowest level of adherence were safety climate and culture of change, and system change. Overall HAI prevalence was 8.06%. A weak to moderate inverse relation was found between IPCAF score and HAI prevalence (Spearman’s Rho -0.340, p 0.034). No other significant correlation was found.ConclusionsThis study found a high self-reported overall level of implementation of multimodal strategies for IPC in the region. Results of this study suggest the relevance of the multimodal approach and the validity of the IPCAF score in measuring IPC programs, in terms of effectiveness of preventing HAI transmission.

A Modeling Analysis of Wastewater Heat Recovery Effects on Wastewater Treatment Plant Nitrification

A global shift towards renewable energy production, driven primarily by the challenges posed by climate change, is currently underway. In this context, the utilization of heat recovery from municipal wastewater emerges as a promising green technology. Notably, the advantage of implementing energy recovery in sewers, as opposed to wastewater treatment plants (WWTPs), lies in the higher temperature of the wastewater and its proximity to potential heat users. Despite these benefits, concerns arise regarding the potential adverse effects on biological wastewater treatment processes downstream of the heat recovery section, particularly during colder seasons. This paper seeks to assess the impact of a heat recovery system along the sewer network on the efficiency of biological wastewater treatment processes. The methodology involves a modeling analysis of a real sewage network in Italy. Under typical northern Italy climate conditions, the results demonstrate the feasibility of heat recovery in sewers for WWTPs designed with a sludge residence time under aerobic conditions (SRTaer) greater than 13 days. In such cases, the nitrification process remains relatively unaffected. However, for lower SRTaer values, a case-specific feasibility assessment is recommended to evaluate the overall process efficiency comprehensively.

Complete genome sequence of invasive Streptococcus pneumoniae serotype 11A causing meningitis in an adult patient, Italy 2022.

Streptococcus pneumoniae is a major global health concern, being a common cause of meningitis in both children and adults. Here, we report the complete genome sequence of P10_PNE_LCR, a S. pneumoniae 11A strain isolated in Northern Italy from an adult patient diagnosed with meningitis.

Exploring multi-antibiotic resistance in Arcobacter butzleri isolates from a poultry processing plant in northern Italy: An in-depth inquiry

Arcobacter butzleri is a foodborne pathogen that has been identified in various animal-derived foods, notably in poultry meat. The prevalence of this bacterium in poultry underscores the need for comprehensive investigations into its dissemination within poultry meat processing plants. Such assessments are critical due to the potential cross-contamination that may occur, impacting the safety of the final food product. This study endeavours to evaluate the genomic similarity of 56 A. butzleri isolates obtained from chicken carcasses (specifically neck skins and caecum, post-slaughter) and equipment surfaces following cleaning and sanitizing procedures. All samples originate from a poultry slaughterhouse in Northern Italy. The genomic analysis includes single nucleotide polymorphism, average nucleotide identity, and core genome multi-locus sequence typing analysis, aiming to discern potential cross-contamination between carcasses and equipment. The study evaluates antibiotic resistance, biofilm production, and host cell colonization of A. butzleri strains through in vitro assays. Genomic de-replication reveals the presence of 31 distinct strains. Results elucidate that a portion of these strains is evident in multiple sources, indicative of cross-contamination even post-cleaning and sanitization. The in vitro tests underline multi-antibiotic resistance of A. butzleri with genes associated with antibiotic resistance, among them mexAB-oprM, showing a correlation to the observed resistance. This study establishes the colonization capability of A. butzleri strains on a human gut mucus-secreting cell model, suggesting a potential virulence factor. Detection of various putative virulence genes further supports the hypothesis of strains virulence potential. This study holds importance of A. butzleri as it unveils the antibiotic resistance and pathogenic capabilities inherent in this species, identifying associated genetic traits. Through comprehensive genomic analysis, it was conclusively validated instances of cross-contamination between various sources and equipment surfaces, underscoring the pervasive dissemination of this bacterium within a food processing plant and its persistence. This research serves as an exploration into the intricate dynamics of A. butzleri within poultry processing environments. It accentuates the imperative for stringent hygiene protocols and ongoing surveillance to curtail the risk of cross-contamination, thereby ensuring the safety of poultry products for discerning consumers.

Modeling the Effect of Temperature on the Severity of Blueberry Stem Blight and Dieback with a Focus on Neofusicoccum parvum and Cultivar Susceptibility

Stem blight and dieback rank among the most relevant diseases affecting blueberry production worldwide. In Northern Italy, Neofusicoccum parvum, Diaporthe rudis, Cadophora luteo-olivacea and Peroneutypa scoparia have been reported to cause stem blight and dieback in blueberry. Considering that the incidence and severity of these diseases are on the rise in Northern Italy, two of the main aims of the present study were a—to compare the in vitro growth rate of the four fungi at different temperatures and b—to assess the aggressiveness of the same fungi on four commercial blueberry cultivars. Neofusicoccum parvum had the fastest growth rate and was the most aggressive pathogen. A possible effect of temperature on host colonization by N. parvum and disease expression was postulated and tested as a third aim. In planta trials were performed to model and predict the influence of temperature on the severity of blueberry stem blight and dieback caused by N. parvum. Increasing temperatures boosted the aggressiveness of the pathogen, causing higher disease severity and host mortality. Our findings suggest that temperature plays a relevant role in the severity of blueberry stem blight and dieback caused by N. parvum. Given the predictions of a warmer climate, this disease may become increasingly more significant and should be actively managed.

A risk-based quantitative approach for priority assessment of ageing bridges accounting for deterioration

The significant role of bridges in transportation networks requires continuous improvement of bridge management strategies, which has been even more exacerbated by the recent bridge collapses worldwide. This study proposes a framework for the prioritization and preliminary risk assessment of existing bridges subjected to seismic and traffic hazards. The proposed method adopts quantitative expressions to define risk in a simplified manner and, consequently, the priority associated with a certain bridge within a bridge stock. The three primary components of risk are considered: vulnerability, exposure, and hazard, which are specified according to the characteristics of the bridge, site, and road network. The bridge state of conservation is accounted for in the vulnerability component through average and critical defect condition indicators. The proposed method is implemented in a case-study of thirty real bridges in northern Italy. The impact of defects on vulnerability and priority ranking of bridges, the assumptions for defects condition and each subcomponent’s contribution to risk classification are discussed. The prioritization results are presented in absolute and normalized formats, with the latter providing a clearer view of the bridges’ relative priority within the stock. Finally, the proposed method’s findings are compared with the current Italian qualitative guidelines for bridge management.

How Criminal Organizations Expand to Strong States: Local Agreements and Migrant Exploitation in Northern Italy

How Criminal Organizations Expand to Strong States: Local Agreements and Migrant Exploitation in Northern Italy

Study of the Roman theatre of Volterra: Acoustic effects based on the presence of different architectural construction elements

Roman theatres have always been the subject of research studies, from an architectural perspective and archaeology. The border lines between these and other disciplines is always difficult to be established since the interrelation of various expertise is required to achieve a complete knowledge of ancient buildings, especially when documentations and archaeological sources are limited. The present work deals with the acoustic analysis of the Roman theatre of Volterra, located in northern Italy, which has already been the subject of archaeological and architectural studies since its discovery in 1950. Acoustic measurements have been carried out in line with the standard requirements outlined in ISO 3382. After model calibration, the acoustic simulations have been carried out using four specific scenarios, highlighting the contribution that different construction elements can have on the acoustic response of this open-air theatre in comparison with the existing conditions. The results were evaluated assuming that light music (classical quartets, unamplified) and prose are the main functions of the space, as this case was in the past. The simulated results show that the values for the main acoustic parameters are better than the measured values, to be closer to the optimal ranges of the criteria borrowed from studies on enclosed spaces, since there are no criteria for Roman theatres. The good acoustic response of the Roman theatre of Volterra raises new doubts about the function of the vessels that were located under the steps of the cavea, as mentioned by Vitruvius.

Increased reports of measles in the Metropolitan City of Milan, northern Italy, September 2023 to March 2024.

Since late 2023, the Metropolitan City of Milan and surrounding areas (northern Italy) have been experiencing a resurgence of measles, with most cases detected starting from January 2024. During this brief period, we observed measles in travellers from endemic areas, participants in international events, vaccinees and healthcare workers. Indigenous cases have also been identified. Even though we have not yet identified large and disruptive outbreaks, strengthening surveillance and vaccination activities is pivotal to help limit the impact of measles spread.

A real-world retrospective-prospective analysis of efficacy and safety of combined ixazomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma: The northern Italy experience.

Ixazomib, lenalidomide, and dexamethasone (IRd) have been approved for the treatment of relapsed/refractory multiple myeloma (RRMM) based on the results of the TOURMALINE-MM1. We conducted a retrospective-prospective analysis of 106 RRMM patients (pts) treated with IRd in 21 centers in Northern Italy, with the aim to evaluate the efficacy and safety of IRd in real life. At IRd initiation, 34% of pts were aged ≥75 (median 72.5), 8.5% had an ECOG performance status ≥2, 54.7% of evaluable pts carried high-risk cytogenetic abnormalities [del17p and/or t(4;14) and/or t(14;16) and/or 1 g gain/amp], 60.2% had received ≥2 prior lines of therapy (pLoT), 57.5% were lenalidomide (Len)-exposed (including both Len-sensitive and Len-refractory pts), and 22% were Len-refractory. Main G ≥3 adverse events (AEs) were thrombocytopenia (16%) and neutropenia (12.3%). G ≥3 non-hematologic AEs included infections (9.4%) and GI toxicity (diarrhea 5.7%, hepatotoxicity 2.8%), VTE, skin rash, and peripheral neuropathy were mainly G1-2. The overall response rate was 56.4% (≥VGPR 30%). With a median follow-up of 38 m, median PFS (mPFS) was 16 m and the 1-year OS rate was 73%. By subgroup analysis, an extended PFS was observed for pts achieving ≥VGPR (mPFS 21.2 m), time from diagnosis to IRd ≥5 years (26.2 m), 1 pLoT (34.4 m), Len-naïve (NR), age ≥70 (20 m). In pts exposed to Len, non-refractory in any prior line and immediately prior to IRd, mPFS was 16 and 18 m, respectively. An inferior PFS was seen in Len-refractory pts (4.6 m). By multivariate analysis, independent predictors of PFS were age ≥70 (HR 0.6), time from diagnosis ≥5 years (HR 0.32), refractoriness to Len in any prior line (HR 3.33), and immediately prior (HR 4.31). IRd might be effective and safe in RRMM pts with an indolent disease, in early lines of treatment, and who proved Len-sensitive, independent of age, and cytogenetic risk.

Molecular phylogenetic analysis of Echinococcus granulosus sensu lato infecting sheep in Italy.

Cystic Echinococcosis (CE), caused by the larval form of Echinococcus granulosus sensu lato, is a neglected zoonosis still threatening public health worldwide. In Italy different epidemiological scenarios were reported depending on the geographical area and associated socio-economic activities. Although in northern Italy the occurrence of E. granulosus is considered sporadic, in the southern regions and, particularly in Sardinia, CE prevalence reaches high levels. We analysed CE cysts collected from infected sheep from various areas of mainland Italy and the Sardinia island, with the main objective to investigate intergenotypic and intragenotypic variations at national level. CE cysts were collected from slaughtered sheep following post mortem inspection at local abattoirs. Total genomic DNA was extracted and amplification and sequencing of the partial mitochondrial genes nad5 and cox1 were performed. A Bayesian phylogenetic tree was estimated on a nad5 dataset (n=260) composed of E. granulosus samples from this study (n=126) and all the nad5 haplotypes available in GenBank (n=134). In addition, haplotype network, diversity and neutrality analysis were performed on nad5 and cox1 sequences of Italian origin obtained in this study. E. granulosus sensu stricto (s.s.) was found to be the only Echinococcus species infecting sheep in Italy, mainly represented by G1 genotype (76%) and, to a lower extent, by G3 genotype (24%). Phylogenetic analyses revealed 40 nad5 and 33 cox 1 haplotypes, and the presence of two founder haplotypes, belonging to G1 and G3 genotype, showing 100% similarity with DNA sequences from different geographic regions. The lack of geographical segregation, high haplotype and low nucleotide diversity coupled with significant negative values of Tajima's D and Fu's Fs observed in this study indicated high genetic variation and demographic expansion of E. granulosus s.s. in Italy.

Elevated NET, Calprotectin, and Neopterin Levels Discriminate between Disease Activity in COVID-19, as Evidenced by Need for Hospitalization among Patients in Northern Italy.

Coronavirus disease 2019 (COVID-19) displays clinical heterogeneity, but little information is available for patients with mild or very early disease. We aimed to characterize biomarkers that are useful for discriminating the hospitalization risk in a COVID-19 cohort from Northern Italy during the first pandemic wave. We enrolled and followed for four weeks 76 symptomatic SARS-CoV-2 positive patients and age/sex-matched healthy controls. Patients with mild disease were discharged (n.42), and the remaining patients were hospitalized (n.34). Blood was collected before any anti-inflammatory/immunosuppressive therapy and assessed for soluble C5b-9/C5a, H3-neutrophil extracellular traps (NETs), calprotectin, and DNase plasma levels via ELISA and a panel of proinflammatory cytokines via ELLA. Calprotectin and NET levels discriminate between hospitalized and non-hospitalized patients, while DNase negatively correlates with NET levels; there are positive correlations between calprotectin and both NET and neopterin levels. Neopterin levels increase in patients at the beginning of the disease and do so more in hospitalized than non-hospitalized patients. C5a and sC5b-9, and other acute phase proteins, correlate with neopterin, calprotectin, and DNase. Both NET and neopterin levels negatively correlate with platelet count. We show that calprotectin, NETs, and neopterin are important proinflammatory parameters potentially useful for discriminating between COVID-19 patients at risk of hospitalization.

Effectiveness of Copeptin, MR-proADM and MR-proANP in Predicting Adverse Outcomes, Alone and in Combination with Traditional Severity Scores, a Secondary Analysis in COVID-19 Patients Requiring Intensive Care Admission.

Objective: To investigate whether copeptin, MR-proADM and MR-proANP, alone or integrated with the SOFA, MuLBSTA and SAPS II scores, are capable of early recognition of COVID-19 ICU patients at increased risk of adverse outcomes. Methods: For this predefined secondary analysis of a larger cohort previously described, all consecutive COVID-19 adult patients admitted between March and December 2020 to the ICU of a referral, university hospital in Northern Italy were screened, and clinical severity scores were calculated upon admission. A blood sample for copeptin, MR-proADM and MR-proANP was collected within 48 h (T1), on day 3 (T3) and 7 (T7). Outcomes considered were ICU and in-hospital mortality, bacterial superinfection, recourse to renal replacement therapy (RRT) or veno-venous extracorporeal membrane oxygenation, need for invasive mechanical ventilation (IMV) and pronation. Results: Sixty-eight patients were enrolled, and in-hospital mortality was 69.1%. ICU mortality was predicted by MR-proANP measured at T1 (HR 1.005, 95% CI 1.001-1.010, p = 0.049), although significance was lost if the analysis was adjusted for procalcitonin and steroid treatment (p = 0.056). Non-survivors showed higher MR-proADM levels than survivors at all time points, and an increase in the ratio between values at baseline and at T7 > 4.9% resulted in a more than four-fold greater risk of in-hospital mortality (HR 4.417, p < 0.001). Finally, when considering patients with any reduction in glomerular filtration, an early copeptin level > 23.4 pmol/L correlated with a more than five-fold higher risk of requiring RRT during hospitalization (HR 5.305, p = 0.044). Conclusion: Timely evaluation of MR-proADM, MR-proANP and copeptin, as well as changes in the former over time, might predict mortality and other adverse outcomes in ICU patients suffering from severe COVID-19.

Polypharmacy, drug-drug interactions, anticholinergic burden and cognitive outcomes: a snapshot from a community-dwelling sample of older men and women in northern Italy

Polypharmacy (PP) use is very common in older people and may lead to drug-drug interactions (DDIs) and anticholinergic burden (ACB) that may affect cognitive function. We aimed to determine the occurrence of PP, potential DDIs and ACB and their role in cognitive outcomes in an older population. Cross-sectional data from 636 community-dwelling adults (73.2 ± 6.0 SD, 58.6% women) participating in the NutBrain study (2019–2023) were analyzed. Participants were asked about their medication use, and data on potential DDIs and ACB were extracted. The associations of PP (≥ 5 drugs/day), potential DDIs, and ACB with mild cognitive impairment (MCI) and specific cognitive domains were assessed using logistic regression adjusted for confounders. Sex-stratified analysis was performed. Overall, 27.2% of the participants were exposed to PP, 42.3% to potential DDIs and 19% to cumulative ACB. Women were less exposed to PP and more exposed to ACB than men. In multivariate analysis, the odds of having MCI (24%) were three times higher in those with severe ACB (≥ 3) (OR 3.34, 95%CI 1.35–8.25). ACB was positively associated with poor executive function (OR 4.45, 95%CI 1.72–11.49) and specifically with the Frontal Assessment Battery and neuropsychological tests of phonological and semantic fluency. In sex-stratified analysis, ACB was statistically significantly associated with MCI and executive function in women and with memory in men. PP, potential DDIs and anticholinergics use are very common in community-dwelling older people. ACB exposure is associated with MCI, particularly with poor executive function. Clinicians are encouraged to be vigilant when prescribing anticholinergics.Trial registration: Trial registration number NCT04461951, date of registration July 7, 2020 (retrospectively registered, ClinicalTrials.gov).