Search

Abstract The objective of this study is to ascertain whether subvalvular papillary muscle repair in conjunction with restrictive mitral valve annuloplasty represents the most efficacious treatment for patients presenting with secondary ischemic mitral regurgitation, as compared to restrictive mitral valve annuloplasty alone and to mitral valve replacement. A network meta-analysis was conducted to investigate outcomes of randomized controlled trials, propensity-matched studies, and observational studies, comparing various treatments for secondary ischemic mitral regurgitation. The average follow-up duration for late mortality was 4.4 years. Coronary artery bypass grafting (CABG) without mitral valve surgery had a late mortality incidence of 3.7%. Restrictive mitral annuloplasty demonstrated a rate of 6.5%, while restrictive mitral annuloplasty + CABG resulted in a rate of 4.1%. Subvalvular papillary muscle repair plus restrictive mitral annuloplasty ± CABG and mitral valve replacement + CABG had rates of 4.4% and 5.1%. SUCRA analysis showed that CABG was the most effective treatment for reducing late mortality (70.0%). This was followed by subvalvular papillary muscle repair plus restrictive mitral annuloplasty with or without CABG (62.4%). The top strategy for decreasing early death, reoperation, and readmission to the hospital for heart failure is subvalvular papillary muscle repair plus restrictive mitral annuloplasty with or without CABG, based on SUCRA probabilities (84.6%, 85.54%, and 86.3%, respectively). Subvalvular papillary muscle repair plus restrictive mitral annuloplasty ± CABG has potential to reduce the risks associated with early mortality, reoperation, and re-hospitalization for heart failure. However, further research is required to substantiate these findings.

Abstract Macroecologists traditionally emphasized the role of environmental variables for predicting species distribution and abundance at large scale. While biotic factors have been increasingly recognized as important at macroecological scales, producing valuable biotic variables remains challenging and rarely tested. Capitalizing on the wealth of population density estimates available for African savannah ungulates, here we modeled species average population density at 100 × 100 km as a function of both environmental variables and proxies of biotic interactions (competition and predation) and estimated their relative contribution. We fitted a linear mixed effect model on 1043 population density estimates for 63 species of ungulates using Bayesian inference and estimated the percentage of total variance explained by environmental, anthropogenic, and biotic interactions variables. Environmental and anthropogenic variables were the main drivers of ungulate population density, with NDVI, Distance to permanent water bodies and Human population density showing the highest contribution to the variance. Nonetheless, biotic interactions altogether contributed to a quarter of the variance explained, with predation and competition having a negative effect on species density. Despite the limitations of modelling biotic interactions in macroecological studies, proxies of biotic interactions can enhance our understanding of biological patterns at broad spatial scales, uncovering novel predictors as well as enhancing the predictive power of large-scale models.

Abstract Background The positive effects of active and passive music activities on older people with dementia are well and largely documented by the literature. Nevertheless, the use of music as a non-pharmacological intervention is not so common both in private and public older people care facilities because in-home staff have no competencies for delivering such activities. Conversely, the realization and implementation of a co-designed music-based curriculum for dementia care professionals may help the diffusion of music in the older people care facilities. This study was aimed at evaluating the learning outcomes of the SOUND training, based on an original co-designed music-based curriculum for dementia care professionals and implemented in Italy, Portugal and Romania. Methods The SOUND training study was developed through three phases: a) the co-design of the music-based curriculum for dementia care professionals, involving 55 people in the three participating countries; b) the teaching of the training curriculum to 63 dementia care professionals (29 in Italy, 17 in Portugal and 17 in Romania), delivered both in person and via a Moodle platform named Virtual Music Circle; c) the learning outcomes assessment, carried out by means of 13 self-evaluation tests, and a practical test, and the trainees’ course evaluation by a questionnaire. Results Most of the trainees reached the highest score in the evaluation of the theoretical competencies in the three study countries. Conversely, some practical competencies in the facilitation of music activities need to be fine-tuned. The SOUND training course was evaluated very positively in the overall structure, theoretical contents, and practical workshops by the trainees. Nevertheless, they preferred the face-to-face compared to the distance learning methodology in the three countries. Conclusions The SOUND training curriculum was effective in teaching music techniques and neurocognitive knowledge to dementia care professionals. Nevertheless, future courses should be differentiated for dementia care professionals with or without previous music knowledge and competencies. Moreover, the course is fully sustainable, because it does not require additional costs given that the curriculum is fully accessible online and it is also replicable because it trains professionals who can continue to apply the method in their working routine.

Aim To compare the need for intubation and mechanical ventilation after surfactant delivery between less invasive surfactant administration (LISA)-treated and intuba-tion-surfactant-extubation (IN-SURE)-treated premature infants with respiratory distress syndrome (RDS). Methods Retrospective registry-based cohort study enrolled 36 newborns admitted to the Neo-natal Intensive Care Unit of the “Santa Maria” Hospital of Terni between 2016 and 2023. As a primary outcome, the need for intubation and mechanical ventilation within 72 hours of life was followed, and major neonatal morbidities and death before discharge as the secondary outcome. Results The LISA group and the IN-SURE group included 13 and 23 newborns, respectively. Demographic features showed no significant differences between the two groups. The need for mechanical ventilation in the first 72 hours of life was similar in both groups (p>0.99). There were no significant differences in morbidities. Conclusion LISA and INSURE are equally effective modalities for surfactant administration for the treatment of RDS in preterm infants.

Abstract Background Immune checkpoint inhibitors (ICIs), administered alone or combined with chemotherapy, are the standard of care in advanced non-oncogene addicted Non-Small Cell Lung Cancer (NSCLC). Despite these treatments' success, most long-term survival benefit is restricted to approximately 20% of patients, highlighting the need to identify novel biomarkers to optimize treatment strategies. In several solid tumors, immune soluble factors, the activatory CD137+ Tcells, and the immunosuppressive cell subsets Tregs and MDSCs (PMN(Lox1+)-MDSC and M-MDSCs) correlated with responses to ICIs and clinical outcomes thus becoming appealing predictive and prognostic factors. This study investigated the role of distinct CD137+ Tcell subsets, Tregs, MDSCs, and immune-soluble factors in NSCLC patients as possible biomarkers. Methods The levels of T cells, MDSCs and soluble factors were evaluated in 89 metastatic NSCLC patients who underwent ICIs as first- or second-line treatment. T cell analysis was performed by cytoflurimetry evaluating Tregs and different CD137+ Tcell subsets also combined with CD3+, CD8+, PD1+, and Ki67+ markers. Circulating cytokines and immune checkpoints were also evaluated by Luminex analysis. All these parameters were correlated with several clinical factors (age, sex, smoking status, PS and TPS), response to therapy, PFS , and OS . The analyses were conducted in the overall population and in patients treated with ICIs as first-line (naïve patients). Results In both groups of patients, high levels of circulating CD137+ and CD137+PD1+ T cells (total, CD4 and CD8) and the soluble factor LAG3 positively correlated with response to therapy. In naïve patients, PMN(Lox1+)-MDSCs negatively correlated with clinical response, and a high percentage of Tregs was associated with favorable survival. Moreover, the balance between Treg/CD137+ Tcells or PMN(Lox1+)-MDSC/CD137+ Tcells was higher in non-responding patients and was associated with poor survival. CD137+ Tcells and Tregs resulted as two positive independent prognostic factors. Conclusion High levels of CD137+, CD137+PD1+ Tcells and sLAG3 could predict the response to ICIs in NSCLC patients independently by previous therapy. Combining the evaluation of CD137+ Tcells and Tregs also as Treg/CD137+ T cells ratio it is possible to identify naive patients with longer survival.

Introduction: The COVID-19 pandemic posed serious challenges to cancer screening delivery, including cervical cancer. While the impact of the pandemic on deferred screening has been documented, less is known about how clinicians experienced barriers to screening delivery, and, in particular, the role of pre-pandemic barriers to changes reported during the pandemic. Methods: Survey of clinicians who performed ≥ 10 cervical cancer screening tests in 2019 from Mass General Brigham, Kaiser Permanente Washington, and Parkland Health, the healthcare systems participating in the Population-based Research to Optimize the Screening Process (PROSPR II) consortium (administered 10/2020–12/2020, response rate 53.7 %). Results: Prior to the pandemic, clinicians commonly noted barriers to the delivery of cervical cancer screening including lack of staff support (57.6%), interpreters (32.5%), resources to support patients with social barriers to care (61.3%), and discrimination or bias in interactions between staff and patients (31.2%). Clinicians who reported experiencing a given barrier to care before the pandemic were more likely than those who did not experience one to report worsening during the pandemic: lack of staff support (odds ratio 4.70, 95% confidence interval 2.94–7.52); lack of interpreters (8.23, 4.46–15.18); lack of resources to support patients in overcoming social barriers (7.65, 4.41–13.27); and discrimination or bias (6.73, 3.03–14.97). Conclusions: Clinicians from three health systems who deliver cervical cancer screening commonly reported barriers to care. Barriers prior to the pandemic were associated with worsening of barriers during the pandemic. Addressing barriers to cervical cancer screening may promote resilience of care delivery during the next public health emergency.

ABSTRACT Besides the acute injury and trauma-induced macroscopic alterations, the evolution to posttraumatic ankle osteoarthritis (PTOA) is a complex process progressing at the tissue and molecular level. Furthermore, changes in the molecular pathways affect chondrocyte viability. Treatment modalities for PTOA focal or confined disease include innovative techniques. Objective: Our purpose is to increase medical awareness based on scientific evidence of pathophysiology, molecular biology, and treatment of post-traumatic ankle osteoarthritis. Methods: To support the perspectives of the experts, evidence from the scientific literature respected the PRISMA guidelines and the PICOS search strategy was used. We included case-control, cohort, experimental studies and case reports, written in English. Results: The authors were homogeneously exposed to 282 selected abstracts and 114 full articles directly related to post-traumatic osteoarthritis after malleolar fractures. Conclusion: The pathophysiological factors involved in posttraumatic ankle osteoarthritis, such as biological, structural, mechanical, and molecular changes must be studied together, as the interaction between these factors determines the risk of progression of PTOA. Inhibition of a single catabolic molecule or cascade probably is not sufficient to alter the natural progression of the pathological process. Evidence level V, expert opinion.

Introduzione e obiettivo L’osteoartrosi (OA) è caratterizzata dalla degenerazione della cartilagine che provoca il cedimento strutturale e funzionale delle articolazioni sinoviali, principalmente attraverso un’alterazione regressiva e non infiammatoria della cartilagine. Questa patologia è una delle principali cause di disabilità in tutto il mondo, in gran parte a causa del dolore. L’obiettivo di questo studio è eseguire una revisione sistematica confrontando l’efficacia delle varie terapie riabilitative proposte per questa patologia, studiare l’importanza della prevenzione in soggetti maggiormente esposti ed evidenziare gli interventi di trattamento che apportano maggiori risultati al paziente. Materiali e metodi La ricerca della letteratura, condotta seguendo le linee guida internazionali PRISMA mediante la strategia PICO, è stata effettuata attraverso le banche dati Medline (via PubMed), Scopus, PEDro, LILACS e Trip Databse tra i mesi di Maggio e Giugno 2023. La letteratura presente è stata vagliata mediante la formulazione di diverse stringhe di ricerca: PubMed ((“Osteoarthrosis” [MeSH]) AND (“physiotherapy” [MeSH] OR (“rehabilitation” [MeSH] OR (“exercise” [MeSH])), Scopus, LILACS e Trip Database (“Osteoarthrosis” AND (“physiotherapy” OR “rehabilitation” OR “ exercise”)) e su PEDro è stata utilizzata la stringa “Osteoarthrosis AND Rehabilitation”. Sono stati inclusi solo studi RCT in lingua inglese, pubblicati dal 2013 al 2023 che andassero a prendere in esame l’arto inferiore con un range di età da 55 a 70 anni non operati. Gli articoli duplicati sono stati eliminati mediante il software EndNote. Inizialmente sono stati selezionati gli articoli pertinenti in base al titolo, poi in base alla lettura dell’abstract e infine in base alla lettura del full text. Risultati Dopo l’inclusione sono stati selezionati 6 RCT con una popolazione affetta da osteoartrosi degli arti inferiori. E’ stata valutata la qualità metodologica mediante la scala PEDro. Gli studi inclusi presentano mediamente un punteggio di 7.3. Sono emerse multiple strategie di trattamento: allenamento aerobico, esercizi di stretching dei muscoli dell’anca, esercizi di equilibrio statico e dinamico, esercizi di stabilità e resistenza, elettroterapia, ma è emerso che la maggior parte degli studi inclusi predilige l’esercizio di rinforzo muscolare. Discussione e conclusioni Alla luce dei risultati ottenuti da questa Revisione Sistematica, si ritiene necessario riconoscere gli interventi riabilitativi, attraverso la loro dimensione multidisciplinare, parte fondamentale del trattamento, importanti tanto quanto l’intervento farmacologico, per determinare un rallentamento nella progressione della patologia e un efficace controllo di quest’ultima. L’analisi di questi ultimi ci porta ad affermare che sarebbe necessario ampliare la ricerca tramite follow-up a lungo termine e aumentare la grandezza del campione.

Background: Breast cancer represents one of the leading causes of death among women. Surgery can be effective, but once breast cancer has metastasized, it becomes extremely difficult to treat. Conventional therapies are associated with substantial toxicity and poor efficacy due to tumor heterogeneity, treatment resistance and disease relapse. Moreover, immune checkpoint blockade appears to offer limited benefit in breast cancer. The poor tumor immunogenicity and the immunosuppressive tumor microenvironment result in scarce T-cell infiltration, leading to a low response rate. Thus, there is considerable interest in the development of improved active immunotherapies capable of sensitizing a patient’s immune system against tumor cells. Methods: We evaluated the in vitro anti-tumor activity of a personalized vaccine based on dendritic cells generated in the presence of interferon (IFN)-α and granulocyte-macrophage colony-stimulating factor (IFN-DC) and loaded with an oxidized lysate from autologous tumor cells expanded as 3D organoid culture maintaining faithful tumor antigenic profiles. Results: Our findings demonstrate that stimulation of breast cancer patients’ lymphocytes with autologous IFN-DC led to efficient Th1-biased response and the generation in vitro of potent cytotoxic activity toward the patients’ own tumor cells. Conclusions: This approach can be potentially applied in association with checkpoint blockade and chemotherapy in the design of new combinatorial therapies for breast cancer.

Abstract Background Patient and Public Involvement and Engagement (PPIE) is important to all aspects of health research. However, there are few examples of successful PPIE in statistical methodology research. One of the reasons for this relates to challenges in the identification of individuals interested in statistical methodology research projects, and ambiguities over the importance of PPIE to these projects. Methods This project was conducted between August 2022 and August 2023. The aim is to report the process of the development of an accessible animation to describe what statistical methodology is and the importance of PPIE in statistical methodology research projects. For this, we combined storyboarding and scriptwriting with feedback from PPIE members and researchers. Results After three stages that incorporated feedback from the relevant stakeholders, we produced a final animation about PPIE in statistical methodology. The resulting animation used minimal text, simple animation techniques and was of short duration (

Abstract The NLRP3 inflammasome is an intracellular, multiprotein complex that promotes the auto-catalytic activation of caspase-1 and the subsequent maturation and secretion of the pro-inflammatory cytokines, IL-1β and IL-18. Persistent activation of the NLRP3 inflammasome has been implicated in the pathophysiology of a number of inflammatory and autoimmune diseases, including neuroinflammation, cardiovascular disease, non-alcoholic steatohepatitis, lupus nephritis and severe asthma. Here we describe the preclinical profile of JT002, a novel small molecule inhibitor of the NLRP3 inflammasome. JT002 potently reduced NLRP3-dependent proinflammatory cytokine production across a number of cellular assays and prevented pyroptosis, an inflammatory form of cell death triggered by active caspase-1. JT002 demonstrated in vivo target engagement at therapeutically relevant concentrations when orally dosed in mice and prevented body weight loss and improved inflammatory and fibrotic endpoints in a model of Muckle–Wells syndrome (MWS). In two distinct models of neutrophilic airway inflammation, JT002 treatment significantly reduced airway hyperresponsiveness and airway neutrophilia. These results provide a rationale for the therapeutic targeting of the NLRP3 inflammasome in severe asthma and point to the use of JT002 in a variety of inflammatory disorders.

Abstract Nowadays, treatment of metastatic breast cancer (MBC) has been enriched with novel therapeutical strategies. Metronomic chemotherapy (mCHT) is a continuous and frequent administration of chemotherapy at a lower dose and so whit less toxicity. Thus, this strategy could be attractive for elderly MBC patients. Aim of this analysis is to provide insights into mCHT’s activity in a real-life setting of elderly MBC patients. Data of patients ≥ 75 years old included in VICTOR-6 study were analyzed. VICTOR-6 is a multicentre, Italian, retrospective study, which collected data on mCHT in MBC patients treated between 2011 and 2016. A total of 112 patients were included. At the beginning of mCHT, median age was 81 years (75–98) and in 33% of the patients mCHT was the first line choice. Overall Response Rate (ORR) and Disease Control Rate (DCR) were 27.9% and 79.3%, respectively. Median PFS ranged between 7.6 and 9.1 months, OS between 14.1 and 18.5 months. The most relevant toxicity was the hematological one (24.1%); severe toxicity (grade 3–4) ranged from 0.9% for skin toxicity up to 8% for hematologic one. This is a large study about mCHT in elderly MBC patients, providing insights to be further investigated in this subgroup of frail patients.

Abstract Non-native pests, climate change, and their interactions are likely to alter relationships between trees and tree-associated organisms with consequences for forest health. To understand and predict such changes, factors structuring tree-associated communities need to be determined. Here, we analysed the data consisting of records of insects and fungi collected from dormant twigs from 155 tree species at 51 botanical gardens or arboreta in 32 countries. Generalized dissimilarity models revealed similar relative importance of studied climatic, host-related and geographic factors on differences in tree-associated communities. Mean annual temperature, phylogenetic distance between hosts and geographic distance between locations were the major drivers of dissimilarities. The increasing importance of high temperatures on differences in studied communities indicate that climate change could affect tree-associated organisms directly and indirectly through host range shifts. Insect and fungal communities were more similar between closely related vs. distant hosts suggesting that host range shifts may facilitate the emergence of new pests. Moreover, dissimilarities among tree-associated communities increased with geographic distance indicating that human-mediated transport may serve as a pathway of the introductions of new pests. The results of this study highlight the need to limit the establishment of tree pests and increase the resilience of forest ecosystems to changes in climate.

Stress and discrimination negatively affect quality of life, but social support may buffer their effects. This study aims: (1) to examine the associations between psychological stress, discrimination, and oral health-related quality of life (OHRQoL); and (2) to assess whether social support, stress and discrimination interact to modify their associations with OHRQoL. We used cross-sectional household-based data from a study including 396 individuals aged 14 years and over from families registered for government social benefits in a city in Southern Brazil. OHRQoL was measured with the Oral Impacts on Daily Performance (OIDP) scale; psychological stress was assessed with the Perceived Stress Scale (PSS); social support was assessed based on the number of close relatives or friends of the participant, and discrimination was assessed with a short version of the Everyday Discrimination Scale. Interactions were estimated using the relative excess of risk due to interaction (RERI). Adjusted effects were calculated with logistic regression. The prevalence of oral impacts among people with higher and lower PSS scores was 81.6% and 65.5%, respectively (p < 0.01). Social support was found to have no interactions with stress levels and discrimination. The association between social discrimination and OHRQoL (OIDP score > 0) was OR = 2.03 (95%CI: 1.23; 3.34) among people with a low level of stress, but was OR = 12.6 (95%CI: 1.31; 120.9) among those with higher levels (p = 0.09, for interaction). Individuals who reported experiencing higher levels of psychological stress and discrimination had worse OHRQoL; a synergistic effect with social support was not clear.

Abstract Structural covariance network (SCN) studies on first-episode antipsychotic-naïve psychosis (FEAP) have examined less granular parcellations on one morphometric feature reporting lower network resilience among other findings. We examined SCNs of volume, cortical thickness, and surface area using the Human Connectome Project atlas-based parcellation (n = 358 regions) from 79 FEAP and 68 controls to comprehensively characterize the networks using a descriptive and perturbational network neuroscience approach. Using graph theoretical methods, we examined network integration, segregation, centrality, community structure, and hub distribution across the small-worldness threshold range and correlated them with psychopathology severity. We used simulated nodal “attacks” (removal of nodes and all their edges) to investigate network resilience, calculated DeltaCon similarity scores, and contrasted the removed nodes to characterize the impact of simulated attacks. Compared to controls, FEAP SCN showed higher betweenness centrality (BC) and lower degree in all three morphometric features and disintegrated with fewer attacks with no change in global efficiency. SCNs showed higher similarity score at the first point of disintegration with ≈ 54% top-ranked BC nodes attacked. FEAP communities consisted of fewer prefrontal, auditory and visual regions. Lower BC, and higher clustering and degree, were associated with greater positive and negative symptom severity. Negative symptoms required twice the changes in these metrics. Globally sparse but locally dense network with more nodes of higher centrality in FEAP could result in higher communication cost compared to controls. FEAP network disintegration with fewer attacks suggests lower resilience without impacting efficiency. Greater network disarray underlying negative symptom severity possibly explains the therapeutic challenge.

Abstract The worldwide inequitable access to vaccination claims for a re-assessment of policies that could minimize the COVID-19 burden in low-income countries. Nine months after the launch of the national vaccination program in March 2021, only 3.4% of the Ethiopian population received two doses of COVID-19 vaccine. We used a SARS-CoV-2 transmission model to estimate the level of immunity accrued before the launch of vaccination in the Southwest Shewa Zone (SWSZ) and to evaluate the impact of alternative age priority vaccination targets in a context of limited vaccine supply. The model was informed with available epidemiological evidence and detailed contact data collected across different geographical settings (urban, rural, or remote). We found that, during the first year of the pandemic, the mean proportion of critical cases occurred in SWSZ attributable to infectors under 30 years of age would range between 24.9 and 48.0%, depending on the geographical setting. During the Delta wave, the contribution of this age group in causing critical cases was estimated to increase on average to 66.7–70.6%. Our findings suggest that, when considering the vaccine product available at the time (ChAdOx1 nCoV-19; 65% efficacy against infection after 2 doses), prioritizing the elderly for vaccination remained the best strategy to minimize the disease burden caused by Delta, irrespectively of the number of available doses. Vaccination of all individuals aged ≥ 50 years would have averted 40 (95%PI: 18–60), 90 (95%PI: 61–111), and 62 (95%PI: 21–108) critical cases per 100,000 residents in urban, rural, and remote areas, respectively. Vaccination of all individuals aged ≥ 30 years would have averted an average of 86–152 critical cases per 100,000 individuals, depending on the setting considered. Despite infections among children and young adults likely caused 70% of critical cases during the Delta wave in SWSZ, most vulnerable ages should remain a key priority target for vaccination against COVID-19.

Objective: Analyze the postoperative complications after repairing acute Achilles tendon rupture and compare them according to the surgical approach (open surgery (OS) or minimally invasive surgery (MIS)) and the patient’s comorbidities. Methods: A retrospective analytical study including 154 consecutive patients with an acute Achilles tendon rupture submitted to surgery and divided into OS and MIS cohorts. The following relevant comorbidities were analyzed: obesity, diabetes mellitus, smoking, dyslipidemia, gout, chronic corticosteroid use, connective tissue pathologies, transplant history, cancer treatment patients, and postoperative complications. Results: Seventy-eight patients (50.6%) were treated surgically with an OS technique and 76 (49.4%) with an MIS approach. Twenty patients (13%) had postoperative complications between the two cohorts (OS 11.5%; MIS 14.5%; p = 0.588). No statistically significant difference was found in the logistic regression of the risk of the surgical approaches and complications. Obesity had a significant statistical difference when complications and comorbidities were compared. Conclusions: Patients with obesity have a higher risk of developing postoperative complications with both OS and MIS techniques. No relationship was found between the type of surgical approach and a higher percentage of postoperative complications in treating acute Achilles tendon rupture.

Knowledge of biodiversity is unevenly distributed across the Tree of Life. In the long run, such disparity in awareness unbalances our understanding of life on Earth, influencing policy decisions and the allocation of research and conservation funding. We investigated how humans accumulate knowledge of biodiversity by searching for consistent relationships between scientific (number of publications) and societal (number of views in Wikipedia) interest, and species-level morphological, ecological, and sociocultural factors. Across a random selection of 3019 species spanning 29 Phyla/Divisions, we show that sociocultural factors are the most important correlates of scientific and societal interest in biodiversity, including the fact that a species is useful or harmful to humans, has a common name, and is listed in the International Union for Conservation of Nature Red List. Furthermore, large-bodied, broadly distributed, and taxonomically unique species receive more scientific and societal attention, whereas colorfulness and phylogenetic proximity to humans correlate exclusively with societal attention. These results highlight a favoritism toward limited branches of the Tree of Life, and that scientific and societal priorities in biodiversity research broadly align. This suggests that we may be missing out on key species in our research and conservation agenda simply because they are not on our cultural radar.

In early 2020, Argentina experienced the worst dengue outbreak in its history, concomitant with first-to-date increasing COVID-19 cases. Dengue epidemics in temperate Argentina have already been described as spatially heterogeneous; in the previous 2016 outbreak, transmission occurred 7.3 times more frequently in slums compared to the rest of Buenos Aires City (CABA). These informal settlements have deficient sanitary conditions, precarious housing and high incidence of social vulnerabilities. The purpose of this work was to study the spatio-temporal patterns of the 2020 dengue epidemic in CABA in relation to socio-economic living conditions of its inhabitants and its interaction with the onset of COVID-19. The study considered the period between Jan 1st and May 30th 2020. Dengue and COVID-19 databases were obtained from the National Health Surveillance System; each record was anonymized and geo-localized. The city was divided according to census tracts and grouped in four socio-economic strata: slums, high, mid and low residential. An aligned-rank transform ANOVA was performed to test for differences in the incidence of dengue and COVID-19, and age at death due to COVID-19, among socio-economic strata, four age categories and their interaction. The incidence by cluster was calculated with a distance matrix up to 600 m from the centroid. Spatial joint dengue and COVID-19 risk was estimated by multiplying the nominal risk for each disease, defined from 1 (low) to 5 (high) according to their quantiles. During the study period, 7,175 dengue cases were registered in CABA (incidence rate 23.3 cases per 10,000 inh), 29.2% of which occurred in slums. During the same period, 8,809 cases of COVID-19 were registered (28.6 cases per 10,000 inh); over half (51.4%) occurred in slums, where the median age of cases (29 years old) was lower than in residential areas (42 years old). The mean age of the deceased was 58 years old in slums compared to 79 years old outside. The percentage of deaths in patients under 60 years old was 56% in slums compared to 8% in the rest of the city. The incidence of both diseases was higher in slums than in residential areas for most age categories. Spatial patterns were heterogeneous: dengue presented higher incidence values in the southern sector of the city and the west, and low values in highly urbanized quarters, whereas COVID-19 presented higher values in the east, south, high populated areas and slums. The lowest joint risk clusters were located mainly in high residential areas, whereas high joint risk was observed mainly in the south, some western clusters, the historical part of the city and center north. The social epidemiological perspective of dengue and COVID-19 differed, given that socio environmental heterogeneity influenced the burden of both viruses in a different manner. Despite the overwhelming effect of the COVID-19 pandemic, health care towards other diseases, especially in territories with pre-existing vulnerabilities, should not be unattended.

Abstract The oceanic South Atlantic Convergence Zone (SACZ) has played a major role during South America’s 2021/2022 summer extreme rainy season, being responsible for more than 90% of the precipitation in some regions of Southeast Brazil and in some regions of the Southwestern Atlantic Ocean (SWA). The summer of 2021/2022 was unique and rare and considered an abnormally humid season as verified by official Brazilian Institutes. First, the unusual number of cases of SACZ episodes (seven), was the highest recorded in the last decade. Second, all the cases that occurred were oceanic SACZ that assumed characteristics of an Atmospheric River and produced an excessively anomalous amount of precipitation during this period. Excess precipitation along with the regions located in mountainous and very uneven relief, which by orographic effects favors high precipitation volumes, were responsible for amplifying the observed impacts, such as landslides and floods that caused several losses to society. We also showed the main effects of coupling and interaction between the waters of the surface layer of the SWA and the atmosphere. Our learning from this study ends with the unprecedented results of how the marine atmospheric boundary layer (MABL) is locally modulated by the sea surface temperature (SST) that lies just below it. Until the present moment, we emphasize that this important mechanism has not been widely highlighted in the literature, showing that even though the ocean is colder than before oceanic SACZ is established, it is still warmer than the overlying air, thus, the ocean continues to be an active source of heat and moisture for the atmosphere and enhances the MABL instability process.

Abstract Acute caffeine intake has been found to increase working memory (WM)-related brain activity in healthy adults without improving behavioral performances. The impact of daily caffeine intake—a ritual shared by 80% of the population worldwide—and of its discontinuation on working memory and its neural correlates remained unknown. In this double-blind, randomized, crossover study, we examined working memory functions in 20 young healthy non-smokers (age: 26.4 ± 4.0 years; body mass index: 22.7 ± 1.4 kg/m2; and habitual caffeine intake: 474.1 ± 107.5 mg/day) in a 10-day caffeine (150 mg × 3 times/day), a 10-day placebo (3 times/day), and a withdrawal condition (9-day caffeine followed by 1-day placebo). Throughout the 10th day of each condition, participants performed four times a working memory task (N-Back, comprising 3- and 0-back), and task-related blood-oxygen-level-dependent (BOLD) activity was measured in the last session with functional magnetic resonance imaging. Compared to placebo, participants showed a higher error rate and a longer reaction time in 3- against 0-back trials in the caffeine condition; also, in the withdrawal condition we observed a higher error rate compared to placebo. However, task-related BOLD activity, i.e., an increased attention network and decreased default mode network activity in 3- versus 0-back, did not show significant differences among three conditions. Interestingly, irrespective of 3- or 0-back, BOLD activity was reduced in the right hippocampus in the caffeine condition compared to placebo. Adding to the earlier evidence showing increasing cerebral metabolic demands for WM function after acute caffeine intake, our data suggest that such demands might be impeded over daily intake and therefore result in a worse performance. Finally, the reduced hippocampal activity may reflect caffeine-associated hippocampal grey matter plasticity reported in the previous analysis. The findings of this study reveal an adapted neurocognitive response to daily caffeine exposure and highlight the importance of classifying impacts of caffeine on clinical and healthy populations.

Abstract Random walks are common in nature and are at the basis of many different phenomena that span from neutrons and light scattering to the behaviour of animals. Despite the evident differences among all these phenomena, theory predicts that they all share a common fascinating feature known as Invariance Property (IP). In a nutshell, IP means that the mean length of the total path of a random walker inside a closed domain is fixed by the geometry and size of the medium. Such a property has been demonstrated to hold not only in optics, but recently also in the field of biology, by studying the movement of bacteria. However, the range of validity of such a universal property, strictly linked to the fulfilment of equilibrium conditions and to the statistical distributions of the steps of the random walkers, is not trivial and needs to be studied in different contexts, such as in the case of biological entities occupied in random foraging in an open environment. Hence, in this paper the IP in a virtual medium inside an open environment has been studied by using actual movements of animals recorded in nature. In particular, we analysed the behaviour of a grazer mollusc, the chiton Acanthopleura granulata. The results depart from those predicted by the IP when the dimension of the medium increases. Such findings are framed in both the condition of nonequilibrium of the walkers, which is typical of animals in nature, and the characteristics of actual animal movements.

Aim: The aim of this in vitro study is to present a debonding protocol developed to remove a screw-retained, monolithic, zirconia restoration from its titanium-base abutment, and to microscopically evaluate the abutment integrity at both the prosthetic and connection levels. Materials and Methods: A total of 30 samples were tested. Each sample consisted of a monolithic zirconia restoration bonded on a titanium link abutment. Five different shapes were designed and fabricated. Randomly, one-third of the Ti-link abutments were subjected to an anodizing process. Then, all the zirconia samples were bonded to the Ti-link abutments according to a pre-established protocol. Forty-eight hours later, the samples were debonded according to the experimental protocol. The outcomes were evaluated by a visual inspection with an optical microscope, scanning electron microscopy (SEM), and chemical composition analysis. Results: Thirty samples were collected and visually analyzed. Seven samples were randomly evaluated via scanning electron microscopy. In all the examinations, no relevant changes were reported. Chemical composition analysis also relieved no changes in the chemical structure of the titanium. Conclusions: The titanium-base abutments do not alter the structure and properties of the material, not creating phase changes or the birth of oxides such as to induce fragility. Further clinical studies with longer follow-up periods are needed to confirm these preliminary results.

Abstract Background Nephrectomy is considered the backbone of managing patients with localized and selected metastatic renal cell carcinoma (mRCC). The prognostic role of nephrectomy has been widely investigated with cytokines and targeted therapy, but it is still unclear in the immunotherapy era. Methods We investigated the Meet-URO-15 study dataset of 571 pretreated mRCC patients receiving nivolumab as second or further lines about the prognostic role of the previous nephrectomy (received in either the localized or metastatic setting) in the overall population and according to the Meet-URO score groups. Results Patients who underwent nephrectomy showed a significantly reduced risk of death (HR 0.44, 95% CI 0.32–0.60, p

This study aims to compare treatments and outcomes of mechanical complications of acute myocardial infarction (MI) during the Covid-19 and in the pre-Covid-19 era. Electronic databases have been searched for MI mechanical complications during the Covid-19 era and in the previous period from January 1998 to January 2020 (pre-Covid-19 era), until October 2021. To perform a quantitative analysis of non-comparative series, a meta-analysis of proportion has been conducted. Early mortality after surgical treatment was 15.0% while it was significantly higher after conservative treatment (62.4%) (P = 0.026). Early mortality after surgical treatment was seemingly higher in the pre-Covid-19 era but the difference did not reach statistical significance (15.0% vs 38.9%; P = 0.13). Mortality in patients treated conservatively, or turned down for surgery, was lower during the Covid-19 pandemic (62.4% vs 97.7%; P = 0.001). The crude mean prevalence of the use rate of conservative or surgical treatment across the studies during Covid-19 and in the pre-Covid-19 era was comparable. The current increased incidence of MI mechanical complications might be a consequence of delayed presentation or restricted access to hospital facilities. Despite the general negative impact of Covid-19 on cardiac surgery volumes and outcomes and the apparent increase of the incidence of MI complications, the outcomes of their surgical and clinical treatment seem not to have been affected during the pandemic.

Introduction A prescribing cascade occurs when a drug is prescribed to manage the often unrecognised side effect of another drug; these cascades are of particular concern for older adults who are at heightened risk for drug-related harm. It is unknown whether, and to what extent, gender bias influences physician decision-making in the context of prescribing cascades. The aim of this transnational study is to explore the potential impact of physician implicit gender biases on prescribing decisions that may lead to the initiation of prescribing cascades in older men and women in two countries, namely: Canada and Italy.Methods and analysis Male and female primary care physicians at each site will be randomised 1:1 to a case vignette that features either a male or female older patient who presents with concerns consistent with the side effect of a medication they are taking. During individual interviews, while masked to the true purpose of the study, participants will read the vignette and use the think-aloud method to describe their ongoing thought processes as they consider the patient’s concerns and determine a course of action. Interviews will be recorded, transcribed verbatim and thematic analysis will be conducted to highlight differences in decisions in the interviews/transcripts, using a common analytical framework across the sites.Ethics and dissemination This study has received ethics approval at each study site. Verbal informed consent will be received from participants prior to data collection and all data will be deidentified and stored on password-protected servers. Results of this study will be disseminated through peer-reviewed journal articles and presented at relevant national and international conferences.

Principi generali di antimicrobial stewardship S. Tedeschi L’interpretazione dell’antibiogramma E. Carretto La terapia antibiotica empirica della sepsi P. Bocchi, P.G. Giuri, M. Gianfreda, S. Detrenis Il trattamento delle infezioni delle vie urinarie B. Laface, C. Moressa, E. Palaghita, G. Palamà, B. Marchisio, P. Colagrande, M. Giusti Approccio clinico alle polmoniti batteriche M. Galassi, S. Fiorino, F. Lari Le infezioni di cute e tessuti molli S. Spiezia, C. Santini Infezioni fungine in Medicina Interna A. Milia, L. Corbo, F. Pieralli

Background: During the COVID-19 pandemic, reduced access to care services and fear of infection prompted families to increase home care for their older relatives with long-term care needs. This had negative effects on both members of the caring dyad, impacting their quality of life (QoL) and mental well-being. This study investigated the factors that influenced the mental well-being and QoL of 239 dyads, before and after the first pandemic wave in Italy. Methods: Data were collected through a survey on the use of health and social care services and interventions by older care recipients living in the community and their family caregivers. Factors associated with deterioration of mental well-being and QoL in older care recipients (mean age 86.1 years old) and their family caregivers after the pandemic were studied. Results: The importance attached by family caregivers to the skills and training of healthcare professionals was a protective factor against the deterioration in the well-being of older care recipients. Similarly, the importance associated by family caregivers to the help received from healthcare professionals was a protective factor for QoL. Financial hardship of older care recipients was a risk factor for deterioration in caregivers’ mental well-being, while support from other family members was a protective factor for QoL. Conclusions: The presence of attentive healthcare professionals, a supportive family environment, and economic support can reduce the burden on both the caregiver and the older care recipient. These aspects need to be considered in any future emergency situation and when planning care services for community-dwelling older people.

A child’s disability, long-term illness, or mental ill-health is known to affect siblings’ health, social life, school engagement, and quality of life. This article addresses a research gap by its focus on young sibling carers and the impact of providing care to a sibling. A cross-national survey study was conducted in 2018–2019 (Italy, the Netherlands, Slovenia, Sweden, Switzerland, the UK) to examine the incidence of adolescent sibling carers, the extent of care they provide, and their self-reported health, well-being, and school situation. The survey was completed by 7146 adolescents, aged 15–17, and 1444 of them provided care to family members with health-related conditions. Out of these, 286 were identified as Sibling Carers and 668 as Parent Carers, while 181 had both sibling(s) and parent(s) with health-related conditions, and thus were identified as Sibling–Parent Carers. Sibling Carers and Sibling–Parent Carers carried out higher levels of caring activities compared to Parent Carers. They reported both positive aspects of caring, such as increased maturity, and negative aspects, such as mental ill-health, impact on schooling and a lack of support. To reduce the negative aspects of a sibling carer role, it is important to recognise them and to implement early preventive measures and formal support.

Long noncoding RNAs (lncRNAs) are emerging as critical regulators of heart physiology and disease, although the studies unveiling their modes of action are still limited to few examples. We recently identified pCharme, a chromatin-associated lncRNA whose functional knockout in mice results in defective myogenesis and morphological remodeling of the cardiac muscle. Here, we combined Cap-Analysis of Gene Expression (CAGE), single-cell (sc)RNA sequencing, and whole-mount in situ hybridization analyses to study pCharme cardiac expression. Since the early steps of cardiomyogenesis, we found the lncRNA being specifically restricted to cardiomyocytes, where it assists the formation of specific nuclear condensates containing MATR3, as well as important RNAs for cardiac development. In line with the functional significance of these activities, pCharme ablation in mice results in a delayed maturation of cardiomyocytes, which ultimately leads to morphological alterations of the ventricular myocardium. Since congenital anomalies in myocardium are clinically relevant in humans and predispose patients to major complications, the identification of novel genes controlling cardiac morphology becomes crucial. Our study offers unique insights into a novel lncRNA-mediated regulatory mechanism promoting cardiomyocyte maturation and bears relevance to Charme locus for future theranostic applications.

Abstract Quantitative muscle MRI (water-T2 and fat mapping) is being increasingly used to assess disease involvement in muscle disorders, while imaging techniques for assessment of the dynamic and elastic muscle properties have not yet been translated into clinics. In this exploratory study, we quantitatively characterized muscle deformation (strain) in patients affected by facioscapulohumeral muscular dystrophy (FSHD), a prevalent muscular dystrophy, by applying dynamic MRI synchronized with neuromuscular electrical stimulation (NMES). We evaluated the quadriceps muscles in 34 ambulatory patients and 13 healthy controls, at 6-to 12-month time intervals. While a subgroup of patients behaved similarly to controls, for another subgroup the median strain decreased over time (approximately 57% over 1.5 years). Dynamic MRI parameters did not correlate with quantitative MRI. Our results suggest that the evaluation of muscle contraction by NMES-MRI is feasible and could potentially be used to explore the elastic properties and monitor muscle involvement in FSHD and other neuromuscular disorders.

Abstract In localized prostate cancer (PCa), Grade Group (GG) and Gleason Score (GS) have a well-established prognostic role. In metastatic castration resistant prostate cancer (mCRPC), the prognostic role of GS and GG is less defined. In first-line treatment of mCRPC, androgen receptor (AR)-directed drugs (abiraterone acetate, enzalutamide) and docetaxel represent the referring options. There is no evidence that the GS/GG systems can add information to guide the choice between AR-directed drugs and docetaxel in the first-line setting of mCRPC. Nowadays there are no validated biomarkers, which define patients who may benefit or not from hormonal treatments or chemotherapy. Androgen receptor (AR) copy number variations (CNV) are predictive factors of poor response to abiraterone and enzalutamide. There are no available data about the association between AR CNV and GG. In this retrospective study, we analysed the association of the highest GG score with AR CNV and their impact on the clinical outcome of AR-directed drugs and docetaxel as first-line therapy for mCRPC patients. Patients benefit from docetaxel, abiraterone or enzalutamide regardless the GG. However, the presence of GG5 and AR CNV gain identifies a subgroup of patients with poor prognosis, which could benefit from front-line docetaxel instead of AR-directed drugs.

Abstract Multi-purpose crops as maize, rice, soybean, and wheat are key in the debate concerning food, land, water and energy security and sustainability. While strong evidence exists on the effects of climate variability on the production of these crops, so far multifaceted attributes of droughts—magnitude, frequency, duration, and timing—have been tackled mainly separately, for a limited part of the cropping season, or over small regions. Here, a more comprehensive assessment is provided on how droughts with their complex patterns—given by their compound attributes—are consistently related to negative impacts on crop yield on a global scale. Magnitude and frequency of both climate and yield variability are jointly analysed from 1981 to 2016 considering multiscale droughts, i.e., dry conditions occurring with different durations and timings along the whole farming season, through two analogous and standardized indicators enabling comparison among crops, countries, and years. Mainly winter wheat and then spring wheat, soybean and the main maize’s season reveal high susceptibility of yield under more complex drought patterns than previously assessed. The second maize’s season and rice present less marked and more uncertain results, respectively. Overall, southern and eastern Europe, the Americas and sub-Saharan Africa presents multi-crop susceptibility, with eastern Europe, Middle East and Central Asia appearing critical regions for the most vulnerable crop, which is wheat. Finally, yield losses for wheat and soybean clearly worsen when moving from moderate to extreme multiscale droughts.

Prior studies emphasize the value of friends’ support for children/adolescents who have a disability or suffer from mental ill-health or a long-term illness. However, few studies have explored how a caring role affects those young friend carers themselves. This paper addresses a gap in the research by focusing on this hitherto neglected group of young carers to explore the impact of providing care to friends. An online survey was employed for a cross-national study conducted in 2018–2019 in Sweden, Italy, Slovenia, the Netherlands, Switzerland, and the United Kingdom to examine the incidence of adolescent young friend carers, the extent of care they provide, and their self-reported health, well-being, and school situation. The survey was completed by 7146 adolescents, aged 15–17, and 1121 of them provided care to a friend with a health-related condition, most frequently mental ill-health. They carried out high levels of caring activities, and a quarter of them also provided care to a family member. They experienced both positive and negative aspects of caring. Nevertheless, in comparison with adolescents who provided care to family members, they reported more health problems, with a dominance of mental ill-health, and they received lower levels of support. Since adolescent friends play a valuable role for young people with health-related conditions, especially mental ill-health, it is important to find ways of optimizing their caring experiences in order that those adolescents who choose to care for a friend can do so without it having a negative impact on their own mental health, well-being, and life situation.

Purpose of review: Management and Optimization of therapy for lower-risk myelodysplastic syndromes will be reviewed here. Recent findings: Lower-risk MDS typically present with clinical manifestations of anemia, which is the most frequently encountered cytopenia in this setting. While therapy with erythropoietic stimulating agents (ESAs) is used in the vast majority of cases, if correctly selected, some patients do not respond, or become irresponsive to ESAs. Novel agents with very different modes of action show promising clinical results in anemic LR-MDS refractory/relapsed after ESAs. Luspatercept, a TGFbeta family ligand trap, induces nearly 50% of transfusion independence in LR MDS. Another investigational agent showing efficacy and possibly disease modifying activity is the telomerase inhibitor imetelstat. Modulation of dose and schedule of hypomethylating agents, both injectable and oral, is currently being explored, and preliminary results are positive. There is still no standard therapeutic approach for thrombocytopenic and neutropenic LR MDS, although they do represent a smaller proportion of cases. Immunosuppressive treatments, as well as TPO mimetics, could represent a good option in selected MDS cases. Summary: At present, the availability of novel active agents allows the planning of sequential therapy, especially for anemic LR MDS. Better diagnosis and prognostic stratification may allow a more precise and personalized treatment.

Abstract BDNF (brain-derived neurotrophic factor) is present in skeletal muscle, controlling muscular metabolism, strength and regeneration processes. However, there is no consensus on BDNF cellular source. Furthermore, while endothelial tissue expresses BDNF in large amount, whether endothelial cells inside muscle expressed BDNF has never been explored. The aim of the present study was to provide a comprehensive analysis of BDNF localization in rat skeletal muscle. Cellular localization of BDNF and activated Tropomyosin-related kinase B (TrkB) receptors was studied by immunohistochemical analysis on soleus (SOL) and gastrocnemius (GAS). BDNF and activated TrkB levels were also measured in muscle homogenates using Western blot analysis and/or Elisa tests. The results revealed BDNF immunostaining in all cell types examined with a prominent staining in endothelial cells and a stronger staining in type II than type I muscular fibers. Endothelial cells but not other cells displayed easily detectable activated TrkB receptor expression. Levels of BDNF and activated TrkB receptors were higher in SOL than GAS. In conclusion, endothelial cells are an important and still unexplored source of BDNF present in skeletal muscle. Endothelial BDNF expression likely explains why oxidative muscle exhibits higher BDNF levels than glycolytic muscle despite higher the BDNF expression by type II fibers.

ObjectiveTo describe a study protocol for investigating the functional association between posture, spinal balance, ambulatory biomechanics, paraspinal muscle fatigue, paraspinal muscle quality and symptoms in patients with symptomatic lumbar spinal stenosis (sLSS) before and 1-year after elective surgical intervention.DesignSingle-centre prospective, experimental, multimodal (clinical, biomechanical, radiological) study with three instances of data collection: baseline (study visit 1), 6-month follow-up (remote) and 1-year follow-up (study visit 2). Both study visits include an in vivo experiment aiming to elicit paraspinal muscle fatigue for postural assessment in a non-fatigued and fatigued state.Experimental protocolAt baseline and 1-year follow-up, 122 patients with sLSS will be assessed clinically, perform the back-performance scale assessment and complete several patient-reported outcome measure (PROMs) questionnaires regarding overall health, disease-related symptoms and kinesiophobia. Posture and biomechanical parameters (joint kinematics, kinetics, surface electromyography, back curvature) will be recorded using an optoelectronic system and retroreflective markers during different tasks including overground walking and movement assessments before and after a modified Biering-Sørensen test, used to elicit paraspinal muscle fatigue. Measurements of muscle size and quality and the severity of spinal stenosis will be obtained using magnetic resonance imaging (MRI) and sagittal postural alignment data from EOS radiographies. After each study visit, physical activity level will be assessed during 9 days using a wrist-worn activity monitor. In addition, physical activity level and PROMs will be assessed remotely at 6-month follow-up.ConclusionThe multimodal set of data obtained using the study protocol described in this paper will help to expand our current knowledge on the pathophysiology, biomechanics, and treatment outcome of degenerative sLSS. The results of this study may contribute to defining and/or altering patient treatment norms, surgery indication criteria and post-surgery rehabilitation schedules.Trial registrationThe protocol was approved by the regional ethics committee and has been registered at clinicaltrials.gov (NCT05523388).

Objective: There is a renewed interest in Syme amputation (SA) as it is considered a “lower limb salvage” procedure. The aim of this study was to describe the characteristics and evolution of diabetic patients who underwent SA to search for factors that would affect the outcome by comparing a group of patients who had a successful amputation against those who required a major amputation. Methods: Seventeen diabetic patients submitted to non-traumatic SA between 2008 and 2016 were analyzed retrospectively. Results: Eight patients required a higher level of amputation. In this group, six patients continued with the posterior tibial artery (PTA) occluded despite the revascularization, and seven were on dialysis. When assessing the permeability of PTA and dialysis as predictors of failure, they multiplied the risk by 20 (cOR of 24 and 21, respectively). However, after adjusting for both factors, there was only clinical significance. Conclusion: SA in diabetic patients may be an alternative in those with a preserved heel pad tissue vascularization and permeable posterior tibial artery at the time of surgery. Patients on dialysis are likely to fail with this level of amputation. Level of Evidence IV; Therapeutic Studies; Retrospective Cohort Study.

Abstract To determine the association between hyperglycemia, glycated albumin (GlyA) and retinopathy of prematurity (ROP). Prospective study of all infants under ROP screening from March 2017 to July 2019. All demographic, clinical and laboratory data were collected. Glucose was measured at birth and every 8 h for the first week and serum GlyA was evaluated at birth, 1st, 2nd and 4th weeks after birth. Reference range for GlyA was obtained. Univariate logistic regression was used to examine risk factors for ROP followed by multivariate regression. A total of 152 infants were included in the study. Median gestational age was 30 weeks and median birth weight 1240 g. Thirty-three infants (21.7%) had ROP. Hyperglycemia was present in 24 (72.7%) infants diagnosed with any ROP versus 6 (0.05%) in those without ROP. Median GlyA at birth, 1st, 2nd and 4th and respective reference ranges were 8.50% (6.00–12.65), 8.20% (5.32–11.67), 8.00% (5.32–10.00) and 7.90% (5.30–9.00) respectively. After multivariate logistic regression, hyperglycemia but not GlyA, remained a significant risk factor for ROP overpowering the other recognized risk factors (Exp (B) 28.062, 95% CI for Exp(B) 7.881–99.924 p

Este artigo busca refletir, cultural e eticamente, sobre os desafios atuais e futuros da incorporação de novas biotecnologias de diagnóstico e tratamento de câncer no Brasil, bem como seu impacto no acesso e no controle do câncer no país. Para tanto, esta pesquisa parte da problematização da literatura sobre o tema e dos resultados de um estudo, que realizou uma websurvey com especialistas médicos dos setores público e privado brasileiros, associados às dez sociedades oncológicas mais representativas do país, atuantes nas áreas da clínica, cirurgia, radioterapia, patologia e diagnóstico. A discussão do estudo desenvolve-se em torno de três eixos temáticos: conhecimento e expectativas sobre o advento das novas tecnologias para o diagnóstico e tratamento do câncer; considerações estruturais e éticas envolvidas no uso atual e futuro das novas tecnologias; e possíveis cenários associados ao uso e aplicação das novas tecnologias para o diagnóstico e tratamento do câncer. Foram suscitadas algumas questões: novos paradigmas tecnológicos beneficiarão todos os usuários do Sistema Único de Saúde (SUS) ou serão privilégios de poucos? Diminuirão as discrepâncias em termos de oferta de distribuição de serviços, de recursos tecnológicos e de acesso ao diagnóstico e tratamento do câncer? Como diversos segmentos da sociedade poderão participar e influir nesse processo? Que tipos de cenários poderão ainda compor esse quadro? Visando contribuir com o planejamento da atenção ao câncer no Brasil, o artigo finaliza propondo o desenvolvimento de futuras ações a partir de cinco dimensões estratégicas: dimensão econômica; dimensão científica, de inovação e tecnológica; dimensão estrutural; dimensão cultural; e dimensão reguladora.

Objetivo: analisar o conhecimento dos profissionais de saúde da Atenção Básica sobre o preenchimento da Caderneta de Saúde da Criança. Metodologia: Recorte de uma pesquisa ação realizada com 59 profissionais de saúde, sendo sete médicos, dez cirurgiões dentistas e 42 enfermeiros que atuavam na Atenção Básica num município da região central do estado do Rio Grande do Sul. Os dados foram coletados de abril a julho de 2021, por meio de questionário online e analisados conforme Análise Textual Discursiva. Resultados: Emergiram duas categorias: Caderneta de saúde da criança e os aspectos facilitadores do processo de trabalho; Caderneta de saúde da criança e os aspectos que dificultam o processo de trabalho. Conclusão: Considera-se que o documento é atualizado e possibilita um cuidado sistematizado, no entanto, não é preenchido adequadamente por todos os profissionais, pois alguns desconhecem seu conteúdo e não entendem como parte fundamental no atendimento à criança.

Objetivo: analisar as características dos cuidadores familiares de Pessoas com Deficiência no contexto rural. Método: trata-se de um estudo quantitativo, com 219 cuidadores de Pessoas com deficiência, que vivem no contexto rural, em oito municípios do sul do Brasil. Os dados foram coletados no período de setembro de 2018 a junho de 2019, por meio de um questionário com variáveis de caracterização e condições do cuidado e do cuidador. A análise dos dados foi realizada por frequência e comparação de frequência. Resultados: os cuidadores domiciliares são, em sua maioria, mulheres, mães, com idade entre 40-60 anos e com baixa escolaridade. Adoeceram após começar a cuidar, descansam pouco e necessitam melhores condições de saúde para ampliar sua qualidade de vida. Conclusão: no contexto rural as cuidadoras de pessoas com deficiência são, muitas vezes, invisíveis aos serviços de saúde e necessitam ser cuidadas.

Objective To map the recommendations for hospitalised patient safety in the context of the COVID-19 pandemic.Design Scoping review using the method recommended by the Joanna Briggs Institute.Data sources Databases: Medline, SCOPUS, EMBASE, ScienceDirect, LILACS, CINAHL and IBECS; grey literature platform: Google Scholar; and 11 official websites of leading healthcare institutions were searched on 27 April 2021 and updated on 11 April 2022.Eligibility criteria We included documents that present recommendations for the safety of hospitalised patients in the context of the COVID-19 pandemic, published in any language, from 2020 onwards.Data extraction and synthesis Data extraction was performed in pairs with consensus rounds. A descriptive analysis was carried out to present the main characteristics of the articles. Qualitative data from the extraction of recommendations were analysed through content analysis.Results One hundred and twenty-five documents were included. Most papers were identified as expert consensus (n=56, 44.8%). Forty-six recommendations were identified for the safety of hospitalised patients: 17 relating to the reorganisation of health services related to the flow of patients, the management of human and material resources and the reorganisation of the hospital environment; 11 on the approach to the airways and the prevention of the spread of aerosols; 11 related to sanitary and hygiene issues; 4 about proper use of personal protective equipment and 3 for effective communication.Conclusions The recommendations mapped in this scoping review present the best practices produced so far and serve as a basis for planning and implementing good practices to ensure safe hospital care, during and after COVID-19. The engagement of everyone involved in the care of hospitalised patients is essential to consolidate the mapped recommendations and provide dignified, safe and quality care.

Abstract Background Severe immune-related Adverse Events (irAEs) develop in 10–27% of patients treated with Immune-Oncology (IO) [Powles (Lancet 391:748–757, 2018); Galsky (Lancet 395:1547–1557, 2020); Haanen (Ann Oncol 28:119–142, 2017)]. The aim of our study was to evaluate efficacy and clinical outcome of metastatic renal cell carcinoma (mRCC) patients who stopped Immune Checkpoint Inhibitors (ICIs) due to early Grade (G) 3-G4 irAEs. Methods We retrospectively collected data from 204 mRCC patients treated with ICIs in 6 Italian referral centers adhering to the Meet-Uro group, between February 2017 and January 2020. To properly weight the results, patients who did not report early G3–G4 toxicities have been included as control group. Primary endpoint was to evaluate 6 months Progression Free Survival (PFS) after early treatment interruption for Grade (G) 3–4 toxicities compared to the control group. Secondary endpoints were to evaluate Time to treatment failure (TTF) and overall survival (OS) in both groups. All statistical analyses were performed using SPSS software (version 19.00, SPSS, Chicago). Results 18/204 (8.8%) patients had early treatment interruption for serious (G3-G4) irAEs. Early was defined as interruption of IO after only one or two administrations. Immune related nephritis and pancreatitis were the most common irAE that lead to treatment interruption. 6/18 patients received IO-IO combination whereas 12/18 patients antiPD1. In the study group, 12/18 (66.6%) were free from progression at 6 months since IO interruption, TTF was 1.6 months (95% CI 1.6–2.1), mPFS was 7.4 months (95% CI 3.16–11.6) and mOS was 15.5 months (5.1–25.8). In the control group 111/184 (60.3%) patients were free from progression at 6 months, TTF was 4.6 months (95% CI 3.5–5.6), mPFS was 4.6 months (95% CI 3.5–5.6) and mOS was 19.6 months (95% CI 15.1–24.0). In the overall population, mPFS was 5.0 months (95% CI 4.0–5.9) and mOS was 19.6 months (95% CI 15.1–24.0). Conclusions ICIs seem to maintain efficacy even after early interruption due to severe irAE.

Abstract Triage is crucial for patient’s management and estimation of the required intensive care unit (ICU) beds is fundamental for health systems during the COVID-19 pandemic. We assessed whether chest computed tomography (CT) of COVID-19 pneumonia has an incremental role in predicting patient’s admission to ICU. We performed volumetric and texture analysis of the areas of the affected lung in CT of 115 outpatients with COVID-19 infection presenting to the emergency room with dyspnea and unresponsive hypoxyemia. Admission blood laboratory including lymphocyte count, serum lactate dehydrogenase, D-dimer and C-reactive protein and the ratio between the arterial partial pressure of oxygen and inspired oxygen were collected. By calculating the areas under the receiver-operating characteristic curves (AUC), we compared the performance of blood laboratory-arterial gas analyses features alone and combined with the CT features in two hybrid models (Hybrid radiological and Hybrid radiomics)for predicting ICU admission. Following a machine learning approach, 63 patients were allocated to the training and 52 to the validation set. Twenty-nine (25%) of patients were admitted to ICU. The Hybrid radiological model comprising the lung %consolidation performed significantly (p = 0.04) better in predicting ICU admission in the validation (AUC = 0.82; 95% confidence interval 0.73–0.97) set than the blood laboratory-arterial gas analyses features alone (AUC = 0.71; 95% confidence interval 0.56–0.86). A risk calculator for ICU admission was derived and is available at: https://github.com/cgplab/covidapp . The volume of the consolidated lung in CT of patients with COVID-19 pneumonia has a mild but significant incremental value in predicting ICU admission.

Abstract Background The favourable safety profile and the increasing confidence with immune checkpoint inhibitors (ICIs) might have boosted their prescription in frail patients with short life expectancies, who usually are not treated with standard chemotherapy. Methods The present analysis aims to describe clinicians’ attitudes towards ICIs administration during late stages of life within a multicenter cohort of advanced cancer patients treated with single agent PD-1/PD-L1 checkpoint inhibitors in Italy. Results Overall, 1149 patients with advanced cancer who received single agent PD-1/PD-L1 checkpoint inhibitors were screened. The final study population consisted of 567 deceased patients. 166 patients (29.3%) had received ICIs within 30 days of death; among them there was a significantly higher proportion of patients with ECOG-PS ≥ 2 (28.3% vs 11.5%, p

Introducción: El enfisema pulmonar sin obstrucción al flujo aéreo es uno de los espectros clínicos sobre los cuales se puede manifestar la enfermedad pulmonar obstructiva crónica. Objetivo: Comparar pacientes con enfisema pulmonar en tomografía computarizada con y sin obstrucción al flujo aéreo por espirometría. Métodos: Estudio de corte transversal en sujetos mayores de 40 años quienes fueron llevados a espirometría y tomografía de tórax en un centro médico especializado entre los años 2018 a 2020. Se realizó un análisis descriptivo resumiendo las variables cualitativas en frecuencias y porcentajes, y las variables cuantitativas en promedio y desviación estándar si su distribución era normal, y mediana y rango intercuartílico si su distribución no era normal. Resultados: Los sujetos sin enfisema con alteración obstructiva presentaban una mayor exposición al humo de leña con el 62,5 % y menor a tabaquismo con el 29,2 %. La capacidad vital forzada fue menor en los sujetos con enfisema sin alteración obstructiva cuando se comparó con los sujetos que no presentaba enfisema y las pruebas de función pulmonar eran normales, la relación volumen espiratorio forzado en el primer segundo/capacidad vital forzada fue similar en estos últimos 2 grupos. Conclusión: Sujetos con enfisema sin alteración obstructiva espirométrica tienen un antecedente frecuente de tabaquismo, alta frecuencia de disnea y menor frecuencia de tos cuando se compara con pacientes con alteración obstructiva en la función pulmonar, la capacidad vital forzada de los sujetos con enfisema sin obstrucción es menor a la de los sujetos sin enfisema ni obstrucción.