COVID-19 respiratory support outside the ICU's doors. An observational study for a new operative strategy

During the first wave of the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic, we faced a massive clinical and organizational challenge having to manage critically ill patients outside the Intensive Care Unit (ICU). This was due to the significant imbalance between ICU bed availability and the number of patients presenting Acute Hypoxemic Respiratory Failure caused by SARS-CoV-2-related interstitial pneumonia. We therefore needed to perform Non-Invasive Ventilation (NIV) in non-intensive wards to assist these patients and relieve pressure on the ICUs and subsequently implemented a new organizational and clinical model. This study was aimed at evaluating its effectiveness and feasibility

Mutations in Radial Spoke Head Genes and Ultrastructural Cilia Defects in East-European Cohort of Primary Ciliary Dyskinesia Patients

Primary ciliary dyskinesia (PCD) is a rare (1/20,000), multisystem disease with a complex phenotype caused by the impaired motility of cilia/flagella, usually related to ultrastructural defects of these organelles. Mutations in genes encoding radial spoke head (RSPH) proteins, elements of the ciliary ultrastructure, have been recently described. However, the relative involvement of RSPH genes in PCD pathogenesis remained unknown, due to a small number of PCD families examined for mutations in these genes. The purpose of this study was to estimate the involvement of RSPH4A and RSPH9 in PCD pathogenesis among East Europeans (West Slavs), and to shed more light on ultrastructural ciliary defects caused by mutations in these genes. The coding sequences of RSPH4A and RSPH9 were screened in PCD patients from 184 families, using single strand conformational polymorphism analysis and sequencing. Two previously described (Q109X; R490X) and two new RSPH4A mutations (W356X; IVS3_2–5del), in/around exons 1 and 3, were identified; no mutations were found in RSPH9. We estimate that mutations in RSPH4A, but not in RSPH9, are responsible for 2–3% of cases in the East European PCD population (4% in PCD families without situs inversus; 11% in families preselected for microtubular defects). Analysis of the SNP-haplotype background provided insight into the ancestry of repetitively found mutations (Q109X; R490X; IVS3_2–5del), but further studies involving other PCD cohorts are required to elucidate whether these mutations are specific for Slavic people or spread among other European populations. Ultrastructural defects associated with the mutations were analyzed in the transmission electron microscope images; almost half of the ciliary cross-sections examined in patients with RSPH4A mutations had the microtubule transposition phenotype (9+0 and 8+1 pattern). While microtubule transposition was a prevalent ultrastructural defect in cilia from patients with RSPH4A mutations, similar defects were also observed in PCD patients with mutations in other genes

Cytokine and Antioxidant Regulation in the Intestine of the Gray Mouse Lemur (Microcebus murinus) During Torpor

During food shortages, the gray mouse lemur (Microcebus murinus) of Madagascar experiences daily torpor thereby reducing energy expenditures. The present study aimed to understand the impacts of torpor on the immune system and antioxidant response in the gut of these animals. This interaction may be of critical importance given the trade-off between the energetically costly immune response and the need to defend against pathogen entry during hypometabolism. The protein levels of cytokines and antioxidants were measured in the small intestine (duodenum, jejunum, and ileum) and large intestine of aroused and torpid lemurs. While there was a significant decrease of some pro-inflammatory cytokines (IL-6 and TNF-α) in the duodenum and jejunum during torpor as compared to aroused animals, there was no change in anti-inflammatory cytokines. We observed decreased levels of cytokines (IL-12p70 and M-CSF), and several chemokines (MCP-1 and MIP-2) but an increase in MIP-1α in the jejunum of the torpid animals. In addition, we evaluated antioxidant response by examining the protein levels of antioxidant enzymes and total antioxidant capacity provided by metabolites such as glutathione (and others). Our results indicated that levels of antioxidant enzymes did not change between torpor and aroused states, although antioxidant capacity was significantly higher in the ileum during torpor. These data suggest a suppression of the immune response, likely as an energy conservation measure, and a limited role of antioxidant defenses in supporting torpor in lemur intestine

Machine learning in perioperative medicine: a systematic review

Background: Risk stratification plays a central role in anesthetic evaluation. The use of Big Data and machine learning (ML) offers considerable advantages for collection and evaluation of large amounts of complex health-care data. We conducted a systematic review to understand the role of ML in the development of predictive post- surgical outcome models and risk stratification. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we selected the period of the research for studies from 1 January 2015 up to 30 March 2021. A systematic search in Scopus, CINAHL, the Cochrane Library, PubMed, and MeSH databases was performed; the strings of research included different combinations of keywords: “risk prediction,” “surgery,” “machine learning,” “intensive care unit (ICU),” and “anesthesia” “perioperative.” We identified 36 eligible studies. This study evaluates the quality of reporting of prediction models using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) checklist. Results: The most considered outcomes were mortality risk, systemic complications (pulmonary, cardiovascular, acute kidney injury (AKI), etc.), ICU admission, anesthesiologic risk and prolonged length of hospital stay. Not all the study completely followed the TRIPOD checklist, but the quality was overall acceptable with 75% of studies (Rev #2, comm #minor issue) showing an adherence rate to TRIPOD more than 60%. The most frequently used algorithms were gradient boosting (n = 13), random forest (n = 10), logistic regression (LR; n = 7), artificial neural networks (ANNs; n = 6), and support vector machines (SVM; n = 6). Models with best performance were random forest and gradient boosting, with AUC > 0.90. Conclusions: The application of ML in medicine appears to have a great potential. From our analysis, depending on the input features considered and on the specific prediction task, ML algorithms seem effective in outcomes prediction more accurately than validated prognostic scores and traditional statistics. Thus, our review encourages the healthcare domain and artificial intelligence (AI) developers to adopt an interdisciplinary and systemic approach to evaluate the overall impact of AI on perioperative risk assessment and on further health care settings as well

Prevention of recurrent respiratory infections : Inter-society Consensus

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs. Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs