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Increasing evidence supports a central role of the immune system in sepsis, but the current view of how sepsis affects immunity, and vice versa, is still rudimentary. The European Group on Immunology of Sepsis has identified major gaps that should be addressed with high priority, such as understanding how immunological alterations predispose to sepsis, key aspects of the immunopathological events during sepsis, and the long-term consequences of sepsis on patient's immunity. We discuss major unmet topics in those three categories, including the role of key immune cells, the cause of lymphopenia, organ-specific immunology, the dynamics of sepsis-associated immunological alterations, the role of the microbiome, the standardisation of immunological tests, the development of better animal models, and the opportunities offered by immunotherapy. Addressing these gaps should help us to better understand sepsis physiopathology, offering translational opportunities to improve its prevention, diagnosis, and care.

COVID-19 case fatalities surged during the month of March 2020 in Italy, reaching over 10,000 by 28 March 2020. This number exceeds the number of fatalities in China (3,301) recorded from January to March, even though the number of diagnosed cases was similar (85,000 Italy vs. 80,000 China). Case Fatality Rates (CFR) could be somewhat unreliable because the estimation of total case numbers is limited by several factors, including insufficient testing and limitations in test kits and materials, such as NP swabs and PPE for testers. Sero prevalence of SARS-CoV-2 antibodies may help in more accurate estimations of the total number of cases. Nevertheless, the disparity in the differences in the total number of fatalities between Italy and China suggests investigation into several factors, such as demographics, sociological interactions, availability of medical equipment (ICU beds and PPE), variants in immune proteins (e.g., HLA, IFNs), past immunity to related CoVs, and mutations in SARS-CoV-2, could impact survival of severe COVID-19 illness survival and the number of case fatalities.

This study provides a comprehensive overview of the materials and methods used to evaluate the effectiveness of the use of biofeedback in the treatment of aggressive episodes in children and adolescents. Aggressive episodes are common in various disorders and are associated with deficits in emotional processing and impulse control, primarily due to dysfunctions in the amygdala and prefrontal cortex (PFC). These brain regions also regulate physiological arousal, influencing heart rate and other autonomic functions even before aggression manifests. These early signals can be shown to the person (biofeedback) reinforcing therapeutic skills to enhance emotional regulation and reduce aggression. A total of 70 participants will be recruited for a randomized controlled trial (RCT). All participants will receive therapy, although only the intervention group will incorporate biofeedback. The experimental study will be split into three blocks: (1) Home Monitoring: Physiological signals will be recorded using a smartwatch, and aggressive episodes will be captured with a camera; (2) Laboratory Assessment: Participants will attend three sessions, where therapists will induce aggressive reactions, using the video clips recorded at home. Simultaneously, real-time physiological signals will be measured. These sessions will also include relaxation periods before and after the provoked outburst; (3) Therapeutic Intervention: Similar to the laboratory assessment block, therapists will induce aggressive responses in three sessions; however, in this block, participants will receive therapy. Additionally, participants who belong to the intervention group, will include biofeedack in the therapy. Biofeedback is focused on heart rate (HR), heart rate variability (HRV), and skin conductance level (SCL). The CACIA, the Stroop, and other pre- and post-experimental tests. will be used to assess the differences between the control and intervention groups. Emotions play a fundamental role in decision-making, social interactions, and mental health. Emotional dysregulation often leads to aggression, irritability, and anxiety. Showing physiological responses to patients, such as heart rate variability and skin conductance, may improve emotional awareness and regulation. This study aims to verify the effectiveness of including biofeedback in such therapy.

Improved risk stratification and prognosis prediction in sepsis is a critical unmet need. Clinical severity scores and available assays such as blood lactate reflect global illness severity with suboptimal performance, and do not specifically reveal the underlying dysregulation of sepsis. Here, we present prognostic models for 30-day mortality generated independently by three scientific groups by using 12 discovery cohorts containing transcriptomic data collected from primarily community-onset sepsis patients. Predictive performance is validated in five cohorts of community-onset sepsis patients in which the models show summary AUROCs ranging from 0.765–0.89. Similar performance is observed in four cohorts of hospital-acquired sepsis. Combining the new gene-expression-based prognostic models with prior clinical severity scores leads to significant improvement in prediction of 30-day mortality as measured via AUROC and net reclassification improvement index These models provide an opportunity to develop molecular bedside tests that may improve risk stratification and mortality prediction in patients with sepsis. Sepsis is characterized by deregulated host response to infection. Efficient therapies are still needed but a limitation for sepsis treatment is the heterogeneity in patients. Here Sweeney et al. generate prognostic models based on gene expression to improve risk stratification classification and prediction for 30-day mortality of patients.

The deposition of aggregated amyloid-β peptides derived from the pro-amyloidogenic processing of the amyloid precurson protein (APP) into characteristic amyloid plaques (APs) is distinctive to Alzheimer’s disease (AD). Alternative APP processing via the metalloprotease ADAM10 prevents amyloid-β formation. We tested whether downregulation of ADAM10 activity by its secreted endogenous inhibitor secreted-frizzled-related protein 1 (SFRP1) is a common trait of sporadic AD. We demonstrate that SFRP1 is significantly increased in the brain and cerebrospinal fluid of patients with AD, accumulates in APs and binds to amyloid-β, hindering amyloid-β protofibril formation. Sfrp1 overexpression in an AD-like mouse model anticipates the appearance of APs and dystrophic neurites, whereas its genetic inactivation or the infusion of α-SFRP1-neutralizing antibodies favors non-amyloidogenic APP processing. Decreased Sfrp1 function lowers AP accumulation, improves AD-related histopathological traits and prevents long-term potentiation loss and cognitive deficits. Our study unveils SFRP1 as a crucial player in AD pathogenesis and a promising AD therapeutic target.

Pandemic H1N1 influenza A (H1N1pdm) is currently a dominant circulating influenza strain worldwide. Severe cases of H1N1pdm infection are characterized by prolonged activation of the immune response, yet the specific role of inflammatory mediators in disease is poorly understood. The inflammatory cytokine IL-6 has been implicated in both seasonal and severe pandemic H1N1 influenza A (H1N1pdm) infection. Here, we investigated the role of IL-6 in severe H1N1pdm infection. We found IL-6 to be an important feature of the host response in both humans and mice infected with H1N1pdm. Elevated levels of IL-6 were associated with severe disease in patients hospitalized with H1N1pdm infection. Notably, serum IL-6 levels associated strongly with the requirement of critical care admission and were predictive of fatal outcome. In C57BL/6J, BALB/cJ, and B6129SF2/J mice, infection with A/Mexico/4108/2009 (H1N1pdm) consistently triggered severe disease and increased IL-6 levels in both lung and serum. Furthermore, in our lethal C57BL/6J mouse model of H1N1pdm infection, global gene expression analysis indicated a pronounced IL-6 associated inflammatory response. Subsequently, we examined disease and outcome in IL-6 deficient mice infected with H1N1pdm. No significant differences in survival, weight loss, viral load, or pathology were observed between IL-6 deficient and wild-type mice following infection. Taken together, our findings suggest IL-6 may be a potential disease severity biomarker, but may not be a suitable therapeutic target in cases of severe H1N1pdm infection due to our mouse data.

Life expectancy has increased, so the number of people in need of intensive care and attention is also growing. Falls are a major problem for older adult health, mainly because of the consequences they entail. Falls are indeed the second leading cause of unintentional death in the world. The impact on privacy, the cost, low performance, or the need to wear uncomfortable devices are the main causes for the lack of widespread solutions for fall detection and prevention. This work present a solution focused on bedtime that addresses all these causes. Bed exit is one of the most critical moments, especially when the person suffers from a cognitive impairment or has mobility problems. For this reason, this work proposes a system that monitors the position in bed in order to identify risk situations as soon as possible. This system is also combined with an automatic fall detection system. Both systems work together, in real time, offering a comprehensive solution to automatic fall detection and prevention, which is low cost and guarantees user privacy. The proposed system was experimentally validated with young adults. Results show that falls can be detected, in real time, with an accuracy of 93.51%, sensitivity of 92.04% and specificity of 95.45%. Furthermore, risk situations, such as transiting from lying on the bed to sitting on the bed side, are recognized with a 96.60% accuracy, and those where the user exits the bed are recognized with a 100% accuracy.

There is a limited understanding of the pathophysiology of postacute pulmonary sequelae in severe COVID-19. The aim of current study was to define the circulating microRNA (miRNA) profiles associated with pulmonary function and radiologic features in survivors of SARS-CoV-2-induced ARDS. The study included patients who developed ARDS secondary to SARS-CoV-2 infection (n = 167) and a group of infected patients who did not develop ARDS (n = 33). Patients were evaluated 3 months after hospital discharge. The follow-up included a complete pulmonary evaluation and chest computed tomography. Plasma miRNA profiling was performed using RT-qPCR. Random forest was used to construct miRNA signatures associated with lung diffusing capacity for carbon monoxide (D LCO ) and total severity score (TSS). Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted. D LCO  < 80% predicted was observed in 81.8% of the patients. TSS showed a median [P 25 ;P 75 ] of 5 [2;8]. The miRNA model associated with D LCO comprised miR-17-5p, miR-27a-3p, miR-126-3p, miR-146a-5p and miR-495-3p. Concerning radiologic features, a miRNA signature composed by miR-9-5p, miR-21-5p, miR-24-3p and miR-221-3p correlated with TSS values. These associations were not observed in the non-ARDS group. KEGG pathway and GO enrichment analyses provided evidence of molecular mechanisms related not only to profibrotic or anti-inflammatory states but also to cell death, immune response, hypoxia, vascularization, coagulation and viral infection. In conclusion, diffusing capacity and radiological features in survivors from SARS-CoV-2-induced ARDS are associated with specific miRNA profiles. These findings provide novel insights into the possible molecular pathways underlying the pathogenesis of pulmonary sequelae. Trial registration: ClinicalTrials.gov identifier: NCT04457505. . Trial registration: ISRCTN.org identifier: ISRCTN16865246. .

Purpose Humoral immunity proteins—immunoglobulins, complement proteins, and antimicrobial peptides—have key antimicrobial and immunomodulatory functions in sepsis. We hypothesised that their circulating levels are lower in non-survivors, potentially resulting in impaired bacterial clearance and persistent or recurrent infections. Methods We performed a systematic review and meta-analysis evaluating differences in humoral immunity proteins between survivors and non-survivors in adult patients with sepsis. PubMed and Embase were searched without date restrictions. Random-effects meta-analyses were used to estimate pooled standardised mean differences (SMD) with 95% confidence intervals (CI). Sensitivity analyses included data from the MIMIC-IV ICU database, and further supplemented by three proteomic studies. Results Thirty-six studies including 6,330 patients were analysed. Thirteen reported on immunoglobulins, 17 on complement proteins, and 7 on the antimicrobial peptide heparin-binding protein (HBP). Survivors had significantly higher levels of complement proteins C3 (SMD 0.53 [0.07–0.99]) and C4 (SMD 0.51 [0.09–0.94]) compared to non-survivors. Conversely, C4a (SMD − 1.17 [–1.77 to − 0.56]) and IgA (SMD − 0.21 [–0.39 to − 0.03]) were significantly lower in survivors. No differences were found for IgG (SMD 0.00 [–0.18 to 0.18]), IgM (SMD − 0.02 [–0.13 to 0.08]), C5, C5a, or HBP. Sensitivity analyses using MIMIC-IV ( n  = 2,452) and proteomic datasets supported these findings. Proteomic data revealed early depletion of classical complement components (C3, C4B) and regulatory proteins in non-survivors. Conclusion Sepsis non-survivors exhibit lower C3 and C4 levels and higher C4a, consistent with complement activation and/or depletion. Complement proteins may serve as potential biomarkers and therapeutic targets in sepsis.

The COVID-19 pandemic has exposed gaps and areas of need in health systems worldwide. This work aims to map the evidence on COVID-19-related healthcare needs of adult patients, their family members, and the professionals involved in their care during the first year of the pandemic. We searched the databases MEDLINE, Embase, and Web of Science. Two reviewers independently screened titles and abstracts and assessed full texts for eligibility. Disagreements were resolved by consensus. Descriptive data were extracted and inductive qualitative content analysis was used to generate codes and derive overarching themes. Thirty-six studies met inclusion criteria, with the majority reporting needs from the perspective of professionals (35/36). Professionals’ needs were grouped into three main clusters (basic, occupational, and psycho-socio-emotional needs); patients’ needs into four (basic, healthcare, psycho-socio-emotional, and other support needs); and family members’ needs into two (psycho-socio-emotional and communication needs). Transversal needs across subgroups were also identified and grouped into three main clusters (public safety, information and communication, and coordination and support needs). This evidence map provides valuable insight on COVID-19-related healthcare needs. More research is needed to assess first-person perspectives of patients and their families, examine whether needs differ by country or region, and evaluate how needs have evolved over time.