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Clearance of secretions remains a challenge in ventilated patients. Despite high-frequency percussive ventilation (HFPV) showing benefits in patients with cystic fibrosis and neuromuscular disorders, very little is known about its effects on other patient categories. Therefore, we designed a physiological pilot study investigating the effects on lung aeration and gas exchange of short HFPV cycles in tracheostomized patients undergoing mechanical ventilation. Electrical impedance tomography (EIT) was recorded at baseline (T0) by a belt wrapped around the patient's chest, followed by the HFPV cycle lasting 10 min. EIT data was collected again after the HFPV cycle (T1) as well as after 1 h (T2) and 3 h (T3) from T0. Variation from baseline of end-expiratory lung impedance (∆EELI), tidal variation (TIV) and global inhomogeneity index (GI) were computed. Arterial blood was also taken for gas analysis. HFPV cycle significantly improved the ∆EELI at T1, T2 and T3 when compared to baseline (p < 0.05 for all comparisons). The ratio between arterial partial pressure and inspired fraction of oxygen (PaO 2 /FiO 2 ) also increased after the treatment (p < 0.001 for all comparison) whereas TIV (p = 0.132) and GI (p = 0.114) remained unchanged. Short cycles of HFPV superimposed to mechanical ventilation promoted alveolar recruitment, as suggested by improved ∆EELI, and improved oxygenation in tracheostomized patients with high load of secretion.Trial Registration Prospectively registered on www.clinicaltrials.gov (NCT05200507; dated 6th January 2022)., (© 2023. The Author(s).)

Background: Subarachnoid haemorrhage (SAH) is a life-threatening condition with associated brain damage. Moreover, SAH is associated with a massive release of catecholamines, which may promote cardiac injury and dysfunction, possibly leading to haemodynamic instability, which in turn may influence a patient's outcome., Objectives: To study the prevalence of cardiac dysfunction (as assessed by echocardiography) in patients with SAH and its effect on clinical outcomes., Design: Systematic review of observational studies., Data Sources: We performed a systematic search over the last 20 years on MEDLINE and EMBASE databases., Eligibility Criteria: Studies reporting echocardiography findings in adult patients with SAH admitted to intensive care. Primary outcomes were in-hospital mortality and poor neurological outcome according to the presence or absence of cardiac dysfunction., Results: We included a total of 23 studies (4 retrospective) enrolling 3511 patients. The cumulative frequency of cardiac dysfunction was 21% (725 patients), reported as regional wall motion abnormality in the vast majority of studies (63%). Due to the heterogeneity of clinical outcome data reporting, a quantitative analysis was carried out only for in-hospital mortality. Cardiac dysfunction was associated with a higher in-hospital mortality [odds ratio 2.69 (1.64 to 4.41); P  < 0.001; I2 = 63%]. The GRADE of evidence assessment resulted in very low certainty of evidence., Conclusion: About one in five patients with SAH develops cardiac dysfunction, which seems to be associated with higher in-hospital mortality. The consistency of cardiac and neurological data reporting is lacking, reducing the comparability of the studies in this field., (Copyright © 2023 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Noninvasive respiratory support (NIRS) has been extensively used during the COVID-19 surge for patients with acute respiratory failure. However, little data are available about barotrauma during NIRS in patients treated outside the intensive care unit (ICU) setting., Methods: COVIMIX-2 was an ancillary analysis of the previous COVIMIX study, a large multicenter observational work investigating the frequencies of barotrauma (i.e., pneumothorax and pneumomediastinum) in adult patients with COVID-19 interstitial pneumonia. Only patients treated with NIRS outside the ICU were considered. Baseline characteristics, clinical and radiological disease severity, type of ventilatory support used, blood tests and mortality were recorded., Results: In all, 179 patients were included, 60 of them with barotrauma. They were older and had lower BMI than controls ( p < 0.001 and p = 0.045, respectively). Cases had higher respiratory rates and lower PaO 2 /FiO 2 ( p = 0.009 and p < 0.001). The frequency of barotrauma was 0.3% [0.1-1.3%], with older age being a risk factor for barotrauma (OR 1.06, p = 0.015). Alveolar-arterial gradient (A-a) DO 2 was protective against barotrauma (OR 0.92 [0.87-0.99], p = 0.026). Barotrauma required active treatment, with drainage, in only a minority of cases. The type of NIRS was not explicitly related to the development of barotrauma. Still, an escalation of respiratory support from conventional oxygen therapy, high flow nasal cannula to noninvasive respiratory mask was predictive for in-hospital death (OR 15.51, p = 0.001)., Conclusions: COVIMIX-2 showed a low frequency for barotrauma, around 0.3%. The type of NIRS used seems not to increase this risk. Patients with barotrauma were older, with more severe systemic disease, and showed increased mortality.

Fecal microbiota transplantation (FMT) has achieved satisfactory results in preventing the recurrence of Clostridioides difficile infection, but these positive outcomes have only been partially replicated in other diseases. Several factors influence FMT success, including those related to donors and recipients (including diversity and specific composition of the gut microbiome, immune system, and host genetics) as well as to working protocols (fecal amount and number of infusions, route of delivery, and adjuvant treatments). Moreover, initial evidence suggests that the clinical success of FMT may be related to the degree of donor microbial engraftment. The application of cutting-edge technologies for microbiome assessment, along with changes in the current vision of fecal transplants, are expected to improve FMT protocols and outcomes. Here, we review the key determinants of FMT success and insights and strategies that will enable a close integration of lab-based and clinical approaches for increasing FMT success., Competing Interests: Declaration of interests A.G. reports personal fees for consultancy for Eisai S.r.l., 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie S.r.l. Board MRGE, and SanofiS.p.A; personal fees for acting as a speaker for Takeda S.p.A, AbbVie, and Sandoz S.p.A; and personal fees for acting on advisory boards for VSL3 and Eisai. G.C. has received personal fees for acting as an advisor for Ferring Therapeutics. H.S. reports lecture fees, board membership, or consultancy from Amgen, Fresenius, IPSEN, Actial, Astellas, Danone, THAC, biose, BiomX, Eligo, Immusmol, Adare, Nestle, Ferring, MSD, Bledina, Pfizer, Biocodex, BMS, Bromatech, Gilead, Janssen, Mayoli, Roche, Sanofi, Servier, Takeda, Abbvie, has stocks from Enterome bioscience, and is co-founder of Exeliom Biosciences. G.I. has received personal fees for acting as a speaker for Biocodex, Danone, Sofar, Malesci, Metagenics, and Tillotts Pharma and for acting as consultant/advisor for Ferring Therapeutics, Giuliani, Metagenics, and Tillotts Pharma., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The human gut is inhabited by a multitude of bacteria, yeasts, and viruses. A dynamic balance among these microorganisms is associated with the well-being of the human being, and a large body of evidence supports a role of dysbiosis in the pathogenesis of several diseases. Given the importance of the gut microbiota in the preservation of human health, probiotics, prebiotics, synbiotics, and postbiotics have been classically used as strategies to modulate the gut microbiota and achieve beneficial effects for the host. Nonetheless, several molecules not typically included in these categories have demonstrated a role in restoring the equilibrium among the components of the gut microbiota. Among these, rifaximin, as well as other antimicrobial drugs, such as triclosan, or natural compounds (including evodiamine and polyphenols) have common pleiotropic characteristics. On one hand, they suppress the growth of dangerous bacteria while promoting beneficial bacteria in the gut microbiota. On the other hand, they contribute to the regulation of the immune response in the case of dysbiosis by directly influencing the immune system and epithelial cells or by inducing the gut bacteria to produce immune-modulatory compounds, such as short-chain fatty acids. Fecal microbiota transplantation (FMT) has also been investigated as a procedure to restore the equilibrium of the gut microbiota and has shown benefits in many diseases, including inflammatory bowel disease, chronic liver disorders, and extraintestinal autoimmune conditions. One of the most significant limits of the current techniques used to modulate the gut microbiota is the lack of tools that can precisely modulate specific members of complex microbial communities. Novel approaches, including the use of engineered probiotic bacteria or bacteriophage-based therapy, have recently appeared as promising strategies to provide targeted and tailored therapeutic modulation of the gut microbiota, but their role in clinical practice has yet to be clarified. The aim of this review is to discuss the most recently introduced innovations in the field of therapeutic microbiome modulation.

Short-chain fatty acids (SCFAs) play a key role in health and disease, as they regulate gut homeostasis and their deficiency is involved in the pathogenesis of several disorders, including inflammatory bowel diseases, colorectal cancer, and cardiometabolic disorders. SCFAs are metabolites of specific bacterial taxa of the human gut microbiota, and their production is influenced by specific foods or food supplements, mainly prebiotics, by the direct fostering of these taxa. This Review provides an overview of SCFAs' roles and functions, and of SCFA-producing bacteria, from their microbiological characteristics and taxonomy to the biochemical process that lead to the release of SCFAs. Moreover, we will describe the potential therapeutic approaches to boost the levels of SCFAs in the human gut and treat different related diseases.

Helicobacter pylori is a Gram-negative bacterium that is able to colonize the human stomach, whose high prevalence has a major impact on human health, due to its association with several gastric and extra-gastric disorders, including gastric cancer. The gastric microenvironment is deeply affected by H. pylori colonization, with consequent effects on the gastrointestinal microbiota, exerted via the regulation of various factors, including gastric acidity, host immune responses, antimicrobial peptides, and virulence factors. The eradication therapy required to treat H. pylori infection can also have detrimental consequences for the gut microbiota, leading to a decreased alpha diversity. Notably, therapy regimens integrated with probiotics have been shown to reduce the negative effects of antibiotic therapy on the gut microbiota. These eradication therapies combined with probiotics have also higher rates of eradication, when compared to standard treatments, and are associated with reduced side effects, improving the patient's compliance. In light of the deep impact of gut microbiota alterations on human health, the present article aims to provide an overview of the complex interaction between H. pylori and the gastrointestinal microbiota, focusing also on the consequences of eradication therapies and the effects of probiotic supplementation.

Purpose of Review: This review aims to summarize the impact of lung ultrasonography (LUS) on economics and possible impact on patients' outcomes, proven its diagnostic accuracy in patients with acute respiratory failure., Recent Findings: Despite some previous ethical concerns on LUS examination, today this technique has showed several advantages. First, it is now clear that the daily use of LUS can provide a relevant cost reduction in healthcare of patients with acute respiratory failure, while reducing the risk of transport of patients to radiological departments for chest CT scan. In addition, LUS reduces the exposition to x-rays since can replace the bedside chest X-ray examination in many cases. Indeed, LUS is characterized by a diagnostic accuracy that is even superior to portable chest X-ray when performed by well trained personnel. Finally, LUS examination is a useful tool to predict the course of patients with pneumonia, including the need for hospitalization and ICU admission, noninvasive ventilation failure and orotracheal intubation, weaning success, and mortality., Summary: LUS should be implemented not only in Intensive Care Units, but also in other setting like emergency departments. Since most data comes from the recent coronavirus disease 2019 pandemic, further investigations are required in Acute Respiratory Failure of different etiologies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

In this study we evaluated the effect of fluid challenge (FC) administration in elective surgical patients with low or normal blood pressure. Secondarily, we appraised the pharmacodynamic effect of FC in normotensive and hypotensive patients. We assessed five merged datasets of patients with a baseline mean arterial pressure (MAP) above or below 65 mmHg and assessed the changes of systolic, diastolic, mean and dicrotic arterial pressures, dynamic indexes of fluid responsiveness and arterial elastance over a 10-min infusion. The hemodynamic effect was assessed by considering the net area under the curve (AUC), the maximal percentage difference from baseline (d max ), the time when the maximal value was observed (t max ) and change from baseline at 5-min (d 5 ) after FC end. A stroke volume index increase > 10% with respect to the baseline value after FC administration indicated fluid response. Two hundred-seventeen patients were analysed [102 (47.0%) fluid responders]. On average, FC restored a MAP [Formula: see text] 65 mmHg after 5 min. The AUCs and the d max of pressure variables and arterial elastance of hypotensive patients were all significantly greater than normotensive patients. Pressure variables and arterial elastance changes in the hypotensive group were all significantly higher at d 5 as compared to the normotensive group. In hypotensive patients, FC restores a MAP [Formula: see text] 65 mmHg after 5 min from infusion start. The hemodynamic profile of FC in hypotensive and normotensive patients is different; both the magnitude of pressure augmentation and duration is greater in the hypotensive group., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose of Review: Do-not-intubate (DNI) orders are more frequently encountered over time. This widespread diffusion of DNI orders make it essential to develop therapeutic strategies matching patient's and his family willingness. The present review sheds light on the therapeutic approaches employed to support respiratory function of patients with DNI orders., Recent Findings: In DNI patients, several approaches have been described to relieve dyspnoea and address acute respiratory failure (ARF). Despite its extensive use, supplemental oxygen is not so useful in assuring dyspnoea relief. Noninvasive respiratory support (NIRS) is frequently employed to treat ARF in DNI patients. Also, to enhance DNI patients comfort during NIRS, it is worthy to point out the role of analgo-sedative medications. Lastly, a particular aspect concerns the first waves of coronavirus disease 2019 pandemic, when DNI orders have been pursued on factors unrelated to patient's wishes, in the total absence of family support due to the lockdown policy. In this setting, NIRS has been extensively employed in DNI patients with a survival rate of around 20%., Summary: In dealing with DNI patients, the individualization of treatments is of pivotal importance to respect patient's preferences and improve quality of life at the same time., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Diaphragm ultrasound is increasingly used in adults, and more recently in pediatric practice. However, normal diaphragm parameters in healthy infants are unknown. This was a prospective observational pilot study aiming to define the normal diaphragm ultrasound characteristics in healthy infants during the first 6 months of life., Methods: We recruited healthy neonates at 7 to 15 days of life, who were followed until the sixth month of life, undergoing five assessments in different time points. The measurements included diaphragm thickness at end expiration (TEE) and at end inspiration (TEI). The thickening fraction (TF) was calculated as (TEI-TEE)/TEE and expressed as a percentage, and as (TEI-TEE)/TEI., Results: A total of 37 toddlers, 16 of which were females (43.2%), were enrolled. Thirty-four children (91.9%) were of Caucasian ethnicity and the median gestational age was 38.4 (35.7-40) weeks. Normal TEE, TEI, and TF have been provided for each time point., Conclusion: We provided new insight regarding data about thickness and thickening function in healthy children to be used for future physiologic and pathologic pediatric studies.

Advanced respiratory monitoring involves several mini- or noninvasive tools, applicable at bedside, focused on assessing lung aeration and morphology, lung recruitment and overdistention, ventilation-perfusion distribution, inspiratory effort, respiratory drive, respiratory muscle contraction, and patient-ventilator asynchrony, in dealing with acute respiratory failure. Compared to a conventional approach, advanced respiratory monitoring has the potential to provide more insights into the pathologic modifications of lung aeration induced by the underlying disease, follow the response to therapies, and support clinicians in setting up a respiratory support strategy aimed at protecting the lung and respiratory muscles. Thus, in the clinical management of the acute respiratory failure, advanced respiratory monitoring could play a key role when a therapeutic strategy, relying on individualization of the treatments, is adopted., (Copyright © 2023, the American Society of Anesthesiologists. All Rights Reserved.)

Gut microbiota plays a fundamental role within human health, and exerts key functions within the human body. Diet is one of the most powerful modulators of gut microbiota functions and composition. This complex interplay involves also the immune system and the intestinal barrier, highlighting the central role of diet in the pathogenesis and treatment of multiple diseases. In this review article we will paint the landscape of the effects of specific dietary nutrients, and of the detrimental or beneficial outcomes of different dietary patterns, on the composition of human gut microbiota. Moreover, we will discuss the potential application of diet as a therapeutic modulator of gut microbiota, including cutting-edge ways of exploitation, including the use of dietary components as adjuvants to promote microbial engraftment after fecal microbiota transplantation, or personalized nutritional approaches, targeted to the patient microbiome., Competing Interests: Declaration of competing interest A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai. G.C. has received personal fees for acting as advisor for Ferring Therapeutics. G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma. All other authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Investigating the health-related quality of life (HRQoL) after intensive care unit (ICU) discharge is necessary to identify possible modifiable risk factors. The primary aim of this study was to investigate the HRQoL in COVID-19 critically ill patients one year after ICU discharge., Methods: In this multicenter prospective observational study, COVID-19 patients admitted to nine ICUs from 1 March 2020 to 28 February 2021 in Italy were enrolled. One year after ICU discharge, patients were required to fill in short-form health survey 36 (SF-36) and impact of event-revised (IES-R) questionnaire. A multivariate linear or logistic regression analysis to search for factors associated with a lower HRQoL and post-traumatic stress disorded (PTSD) were carried out, respectively., Results: Among 1003 patients screened, 343 (median age 63 years [57-70]) were enrolled. Mechanical ventilation lasted for a median of 10 days [2-20]. Physical functioning (PF 85 [60-95]), physical role (PR 75 [0-100]), emotional role (RE 100 [33-100]), bodily pain (BP 77.5 [45-100]), social functioning (SF 75 [50-100]), general health (GH 55 [35-72]), vitality (VT 55 [40-70]), mental health (MH 68 [52-84]) and health change (HC 50 [25-75]) describe the SF-36 items. A median physical component summary (PCS) and mental component summary (MCS) scores were 45.9 (36.5-53.5) and 51.7 (48.8-54.3), respectively, considering 50 as the normal value of the healthy general population. In all, 109 patients (31.8%) tested positive for post-traumatic stress disorder, also reporting a significantly worse HRQoL in all SF-36 domains. The female gender, history of cardiovascular disease, liver disease and length of hospital stay negatively affected the HRQoL. Weight at follow-up was a risk factor for PTSD (OR 1.02, p = 0.03)., Conclusions: The HRQoL in COVID-19 ARDS (C-ARDS) patients was reduced regarding the PCS, while the median MCS value was slightly above normal. Some risk factors for a lower HRQoL have been identified, the presence of PTSD is one of them. Further research is warranted to better identify the possible factors affecting the HRQoL in C-ARDS.

Background: This single-center preliminary prospective observational study used bedside ultrasound to assess the lung aeration modifications induced by recruitment maneuver and pronation in intubated patients with acute respiratory disease syndrome (ARDS) related to coronavirus 2019 disease (COVID-19). All adult intubated COVID-19 patients suitable for pronation were screened. After enrollment, patients underwent 1 h in a volume-controlled mode in supine position (baseline) followed by a 35-cmH 2 O-recruitment maneuver of 2 min (recruitment). Final step involved volume-controlled mode in prone position set as at baseline (pronation). At the end of the first two steps and 1 h after pronation, a lung ultrasound was performed, and global and regional lung ultrasound score (LUS) were analyzed. Data sets are presented as a median and 25th-75th percentile., Results: From January to May 2022, 20 patients were included and analyzed. Global LUS reduced from 26.5 (23.5-30.0) at baseline to 21.5 (18.0-23.3) and 23.0 (21.0-26.3) at recruitment (p < 0.001) and pronation (p = 0.004). In the anterior lung regions, the regional LUS were 1.8 (1.1-2.0) following recruitment and 2.0 (1.6-2.2) in the supine (p = 0.008) and 2.0 (1.8-2.3) in prone position (p = 0.023). Regional LUS diminished from 2.3 (2.0-2.5) in supine to 2.0 (1.8-2.0) with recruitment in the lateral lung zones (p = 0.036). Finally, in the posterior lung units, regional LUS improved from 2.5 (2.3-2.8) in supine to 2.3 (1.8-2.5) through recruitment (p = 0.003) and 1.8 (1.3-2.2) with pronation (p < 0.0001)., Conclusions: In our investigation, recruitment maneuver and prone positioning demonstrated an enhancement in lung aeration when compared to supine position, as assessed by bedside lung ultrasound., Trial Registration: www., Clinicaltrials: gov , Number NCT05209477, prospectively registered and released on 01/26/2022., (© 2023. The Author(s).)

Competing Interests: Competing interests: GC has received personal fees for acting as advisor for Ferring Therapeutics. GI has received personalfees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant/advisor for Ferring Therapeutics, Giuliani,Metagenics and Tillotts Pharma. QL is a named inventor of patent applications held by MagIC that is related to the treatment of bacterial infection with FMT.

Short bowel syndrome (SBS) with intestinal failure (IF) is a rare but severe complication of Crohn's disease (CD), which is the most frequent benign condition that leads to SBS after repeated surgical resections, even in the era of biologics and small molecules. Glucagon-like peptide-2 analogues have been deeply studied recently for the treatment of SBS-IF. These drugs have a significant intestinotrophic effect and the potential to reduce the chronic dependence of SBS-IF patients on parenteral support or nutrition. Teduglutide has been approved for the treatment of SBS-IF, and apraglutide is currently in clinical development. The use of these drugs was examined with a focus on their use in CD patients., Competing Interests: Conflict-of-interest statement: Guidi L consulted and/or lecture fees: AbbVie, Janssen, Pfizer, Shire, Takeda. All the other authors declare that they have no affiliations with or involvement in any organization or entity with any financial interest in the subject matter or materials discussed in this manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Left ventricular (LV) diastolic dysfunction is a commonly encountered condition and its impact on the anesthesia and the intensive care population is often underestimated. The study of the diastole is known as "diastology" and comprises four phases: isovolumetric relaxation, early filling phase, diastasis, and late filling phase. Diastolic function needs at least the same attention as systolic function, since its alteration has been associated with worse prognosis. Notwithstanding, many physicians consider the assessment of diastolic function too much complex. In this context, the latest 2016 guideline have simplified the assessment of diastolic function. In this educational review, we approach diastolic dysfunction with didactic purposes. First, we use a metaphor to consider the LV as a glass that progressively changes its shape and height along the disease course, resembling variable end-diastolic pressures and volumes at different stages while progressing with diastolic dysfunction. We guide readers in the process of diagnosis and grading of LV diastolic dysfunction, with description of pathophysiological changes in LV relaxation and consequently in the pressure gradient between the left-sided heart chambers. In the second part, starting from physiology we move towards suggestions for the clinical management of anesthesia and intensive care patients with diastolic dysfunction under different scenarios (hypo- and hypervolemia, weaning, sepsis, tachycardia and arrhythmias, right ventricular dysfunction).

Competing Interests: EJK and GC are joint senior authors. GI has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics, and Tillotts Pharma, and for acting as consultant or advisor for Ferring Therapeutics, Giuliani, Malesci, and Tillotts Pharma. BHM has received consultancy fees from Finch Therapeutics Group and Ferring Pharmaceuticals. HS reports personal fees from Danone, Enterome, Takeda, AbbVie, Roche, Amgen, Danone, BiomX, Ferring, BMS, Astellas, MSD, Novartis, Tillotts Pharma, and Biose; grants from Biocodex, Danone, and BiomX; and is a co-founder of Exeliom Biosciences. MJGTV has received research grants from 3M, Astellas Pharma, Biontech, DaVolterra, Evonik, Gilead Sciences, Glycom, Immunic, MaaT Pharma, Merck/MSD, Organobalance, Seres Therapeutics, and Takeda Pharmaceutical, and speaker or consultancy fees from Alb Fils Kliniken, Arderypharm, Astellas Pharma, Basilea, Bio-Mérieux, DaVolterra, Farmak International Holding GmbH, Ferring, Gilead Sciences, Immunic, MaaT Pharma, Merck/MSD, Pfizer, Roche, Organobalance, and SocraTec R&D. AG reports personal fees for consultancy from Eisai, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, Sinergie Srl, Board MRGE, and Sanofi; personal fees for acting as a speaker for Takeda, AbbVie, and Sandoz; and personal fees for acting on advisory boards for VSL3 and Eisai. JJK and EJK have received unrestricted research grants from the Vedanta Biomedical Company, Boston. GC has received personal fees for acting as advisor for Ferring Therapeutics. All other authors declare no competing interests. GI is supported by the Linea D-1 of the Catholic University of Rome and by the Ricerca Finalizzata Giovani Ricercatori 2018 of the Italian Ministry of Health (project GR-2018-12365734) AG, GC, and GI are supported by the BIOMIS grant of the Italian Ministry of Research. BHM is supported by a National Institute of Health Research (NIHR) Academic Clinical Lectureship (CL-2019-21-002). GI, AG, and GC thank the Fondazione Roma for the invaluable support to their scientific research.

Critical care ultrasonography (US) is widely used by intensivists managing critically ill patients to accurately and rapidly assess different clinical scenarios, which include pneumothorax, pleural effusion, pulmonary edema, hydronephrosis, hemoperitoneum, and deep vein thrombosis. Basic and advanced critical care ultrasonographic skills are routinely used to supplement physical examination of critically ill patients, to determine the etiology of critical illness and to guide subsequent therapy. European guidelines now recommend the use of US for a number of practical procedures commonly performed in critical care. Full training and competence acquisition are essential before significant therapeutic decisions are made based on the US assessment. However, there are no universally accepted learning pathways and methodological standards for the acquisition of these skills.Therefore, in this review, we aim to provide a methodological approach of the head to toe ultrasonographic evaluation of critically ill patients considering different districts and clinical applications., (© 2022. The Author(s).)

(1) Background: In COVID-19 patients, the occurrence of thromboembolic complications contributes to disease progression and mortality. In patients at increased risk for thrombotic complications, therapeutic enoxaparin should be considered. However, critically ill COVID-19 patients could develop resistance to enoxaparin. Bivalirudin, a thrombin inhibitor, may be an alternative. This pilot multicenter randomized controlled trial aims to ascertain if bivalirudin may reduce the time spent under invasive mechanical ventilation, as compared to enoxaparin. (2) Methods: Intubated COVID-19 patients at risk for thrombo-embolic complications were randomized to receive therapeutic doses of enoxaparin or bivalirudin. We ascertained the time spent under invasive mechanical ventilation during the first 28 days from Intensive Care Unit (ICU) admission. A standardized weaning protocol was implemented in all centers. In addition, we assessed the occurrence of thromboembolic complications, the number of patients requiring percutaneous tracheostomy, the gas exchange, the reintubation rate, the ICU length of stay, the ICU and 28-days mortalities. (3) Results: We enrolled 58 consecutive patients. Bivalirudin did not reduce the time spent under invasive mechanical ventilation as compared to enoxaparin (12 [8; 13] vs. 13 [10; 15] days, respectively; p = 0.078). Thrombotic ( p = 0.056) and embolic ( p = 0.423) complications, need for tracheostomy ( p = 0.423) or reintubation ( p = 0.999), the ICU length of stay ( p = 0.076) and mortality ( p = 0.777) were also similar between treatments. Patients randomized to bivalirudin showed a higher oxygenation at day 7 and 15 after randomization, when compared to enoxaparin group. (4) Conclusions: In intubated COVID-19 patients at increased risk for thromboembolic complications, bivalirudin did not reduce the time spent under invasive mechanical ventilation, nor improved any other clinical outcomes.

Purpose:  The goal of this survey was to describe the use and diffusion of lung ultrasound (LUS), the level of training received before and during the COVID-19 pandemic, and the clinical impact LUS has had on COVID-19 cases in intensive care units (ICU) from February 2020 to May 2020., Materials and Methods:  The Italian Lung Ultrasound Survey (ITALUS) was a nationwide online survey proposed to Italian anesthesiologists and intensive care physicians carried out after the first wave of the COVID-19 pandemic. It consisted of 27 questions, both quantitative and qualitative., Results:  807 responded to the survey. The median previous LUS experience was 3 years (IQR 1.0-6.0). 473 (60.9 %) reported having attended at least one training course on LUS before the COVID-19 pandemic. 519 (73.9 %) reported knowing how to use the LUS score. 404 (52 %) reported being able to use LUS without any supervision. 479 (68.2 %) said that LUS influenced their clinical decision-making, mostly with respect to patient monitoring. During the pandemic, the median of patients daily evaluated with LUS increased 3-fold (p < 0.001), daily use of general LUS increased from 10.4 % to 28.9 % (p < 0.001), and the daily use of LUS score in particular increased from 1.6 % to 9.0 % (p < 0.001)., Conclusion:  This survey showed that LUS was already extensively used during the first wave of the COVID-19 pandemic by anesthesiologists and intensive care physicians in Italy, and then its adoption increased further. Residency programs are already progressively implementing LUS teaching. However, 76.7 % of the sample did not undertake any LUS certification., Competing Interests: Francesco Mojoli, fee for lectures (Hamilton Medical, GE Healthcare, SEDA Spa). Consultancy agreement between University of Pavia and Hamilton Medical.Silvia Mongodi, received fees for lectures by GE healthcare, outside the present work., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Fecal microbiota transplantation (FMT) is highly effective against recurrent Clostridioides difficile infection and is considered a promising treatment for other microbiome-related disorders, but a comprehensive understanding of microbial engraftment dynamics is lacking, which prevents informed applications of this therapeutic approach. Here, we performed an integrated shotgun metagenomic systematic meta-analysis of new and publicly available stool microbiomes collected from 226 triads of donors, pre-FMT recipients and post-FMT recipients across eight different disease types. By leveraging improved metagenomic strain-profiling to infer strain sharing, we found that recipients with higher donor strain engraftment were more likely to experience clinical success after FMT (P = 0.017) when evaluated across studies. Considering all cohorts, increased engraftment was noted in individuals receiving FMT from multiple routes (for example, both via capsules and colonoscopy during the same treatment) as well as in antibiotic-treated recipients with infectious diseases compared with antibiotic-naïve patients with noncommunicable diseases. Bacteroidetes and Actinobacteria species (including Bifidobacteria) displayed higher engraftment than Firmicutes except for six under-characterized Firmicutes species. Cross-dataset machine learning predicted the presence or absence of species in the post-FMT recipient at 0.77 average AUROC in leave-one-dataset-out evaluation, and highlighted the relevance of microbial abundance, prevalence and taxonomy to infer post-FMT species presence. By exploring the dynamics of microbiome engraftment after FMT and their association with clinical variables, our study uncovered species-specific engraftment patterns and presented machine learning models able to predict donors that might optimize post-FMT specific microbiome characteristics for disease-targeted FMT protocols., (© 2022. The Author(s).)

Background: Diaphragmatic dysfunction is a major factor responsible for weaning failure in patients that underwent prolonged invasive mechanical ventilation for acute severe respiratory failure from COVID-19. This study hypothesizes that ultrasound measured diaphragmatic thickening fraction (DTF) could provide corroborating information for weaning COVID-19 patients from mechanical ventilation., Methods: This was an observational, pragmatic, cross-section, multicenter study in 6 Italian intensive care units. DTF was assessed in COVID-19 patients undergoing weaning from mechanical ventilation from 1st March 2020 to 30th June 2021. Primary aim was to evaluate whether DTF is a predictive factor for weaning failure., Results: Fifty-seven patients were enrolled, 25 patients failed spontaneous breathing trial (44%). Median length of invasive ventilation was 14 days (IQR 7-22). Median DTF within 24 h since the start of weaning was 28% (IQR 22-39%), RASS score (- 2 vs - 2; p = 0.031); Kelly-Matthay score (2 vs 1; p = 0.002); inspiratory oxygen fraction (0.45 vs 0.40; p = 0.033). PaO 2 /FiO 2 ratio was lower (176 vs 241; p = 0.032) and length of intensive care stay was longer (27 vs 16.5 days; p = 0.025) in patients who failed weaning. The generalized linear regression model did not select any variables that could predict weaning failure. DTF was correlated with pH (RR 1.56 × 10 27 ; p = 0.002); Kelly-Matthay score (RR 353; p < 0.001); RASS (RR 2.11; p = 0.003); PaO 2 /FiO 2 ratio (RR 1.03; p = 0.05); SAPS2 (RR 0.71; p = 0.005); hospital and ICU length of stay (RR 1.22 and 0.79, respectively; p < 0.001 and p = 0.004)., Conclusions: DTF in COVID-19 patients was not predictive of weaning failure from mechanical ventilation, and larger studies are needed to evaluate it in clinical practice further. Registered: ClinicalTrial.gov (NCT05019313, 24 August 2021)., (© 2022. The Author(s).)

Fecal microbiota transplantation (FMT) consists of infusion of feces from a donor to a recipient patient in order to restore the resident microbial population. FMT has shown to be a valid clinical option for Clostridioides difficile infections (CDI). However, this approach shows several criticalities, such as the recruiting and screening of voluntary donors. Our aim was to evaluate the therapeutic efficacy of a synthetic bacterial suspension defined "Bacterial Consortium" (BC) infused in the colon of CDI patients. The suspension was composed by 13 microbial species isolated by culturomics protocols from healthy donors' feces. The efficacy of the treatment was assessed both clinically and by metagenomics typing. Fecal samples of the recipient patients were collected before and after infusion. DNA samples obtained from feces at different time points (preinfusion, 7, 15, 30, and 90 days after infusion) were analyzed by next-generation sequencing. Before infusion, patient 1 showed an intestinal microbiota dominated by the phylum Bacteroidetes . Seven days after the infusion, Bacteroidetes decreased, followed by an implementation of Firmicutes and Verrucomicrobia . Patient 2, before infusion, showed a strong abundance of Proteobacteria and a significant deficiency of Bacteroidetes and Verrucomicrobia . Seven days after infusion, Proteobacteria strongly decreased, while Bacteroidetes and Verrucomicrobia increased. Metagenomics data revealed an "awakening" by microbial species absent or low concentrated at time T0 and present after the infusion. In conclusion, the infusion of selected bacteria would act as a trigger factor for "bacterial repopulation" representing an innovative treatment in patients with Clostridioides difficile infections., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Gianluca Quaranta et al.)

Purpose: A number of studies performed in the operating room evaluated the hemodynamic effects of the fluid challenge (FC), solely considering the effect before and after the infusion. Few studies have investigated the pharmacodynamic effect of the FC on hemodynamic flow and pressure variables. We designed this trial aiming at describing the pharmacodynamic profile of two different FC infusion times, of a fixed dose of 4 ml kg -1 ., Methods: Forty-nine elective neurosurgical patients received two consecutive FCs of 4 ml kg -1 of crystalloids in 10 (FC 10 ) or 20 (FC 20 ) minutes, in a random order. Fluid responsiveness was defined as stroke volume index increase ≥ 10%. We assessed the net area under the curve (AUC), the maximal percentage difference from baseline (d max ), time when the d max was observed (t max ), change from baseline at 1-min (d 1 ) and 5-min (d 5 ) after FC end., Results: After FC 10 and FC 20, 25 (51%) and 14 (29%) of 49 patients were classified as fluid responders (p = 0.001). With the exception of the AUCs of SAP and MAP, the AUCs of all the considered hemodynamic variables were comparable. The d max and the t max were overall comparable. In both groups, the hemodynamic effects on flow variables were dissipated within 5 min after FC end., Conclusions: The infusion time of FC administration affects fluid responsiveness, being higher for FC 10 as compared to FC 20 . The effect on flow variables of either FCs fades 5 min after the end of infusion., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Noninvasive respiratory support (NRS) has been used to treat acute respiratory failure outside the ICU, but existing data have left many knowledge gaps for managing NRS in general wards. The primary objective of this study was to describe indications, duration of treatment, and outcomes of subjects treated with NRS outside the ICU. The secondary objective was to compare outcomes based on age < 80 or ≥ 80 y., Methods: This retrospective observational study was conducted at Maggiore della Carità University Hospital in Novara, Italy, and included all patients treated with noninvasive ventilation (NIV) or CPAP outside the ICU from November 2017 to October 2018, with 1 year of follow-up., Results: Of the 570 treatments performed, 383 subjects were analyzed, 136 NIV and 247 CPAP. Subjects' median (interquartile range [IQR]) age was 79 (72-85) y, and the main diagnoses of respiratory failure were cardiogenic pulmonary edema in 128 subjects (33%), pneumonia in 99 (26%), and COPD exacerbation in 52 (14%), with a median (IQR) treatment duration of 38 (16-74) h. Rapid response team visits lasted a median (IQR) 3 (2-6) d. Interface-related pressure lesions occurred in 13% of the subjects, in no case leading to definitive treatment discontinuation. Compared with the subjects ≥ 80 y old, the younger subjects had a median (IQR) longer hospitalization (16 [10-24] d vs 13 [9-20] d; P = .003) but slightly decreased in-hospital mortality (21% vs 30%; P = .061) and a decreased post-discharged 1-year mortality in hospital survivors (25% vs 41%; P = .002), differences observed only in the subjects treated with NIV., Conclusions: In a real-life setting outside the ICU, NIV and CPAP managed by a rapid response team with a daily visit in collaboration with ward staff highly experienced in NRS allowed us to treat the subjects without major complications. Post-discharge 1-year mortality was higher in the subjects ≥ 80 y old treated with NIV for acute hypercapnic respiratory failure., (Copyright © 2022 by Daedalus Enterprises.)

Clostridioides difficile infection (CDI) and inflammatory bowel disease (IBD) are two pathologies that share a bidirectional causal nexus, as CDI is known to have an aggravating effect on IBD and IBD is a known risk factor for CDI. The colonic involvement in IBD not only renders the host more prone to an initial CDI development but also to further recurrences. Furthermore, IBD flares, which are predominantly set off by a CDI, not only create a need for therapy escalation but also prolong hospital stay. For these reasons, adequate and comprehensive management of CDI is of paramount importance in patients with IBD. Microbiological diagnosis, correct evaluation of clinical status, and consideration of different treatment options (from antibiotics and fecal microbiota transplantation to monoclonal antibodies) carry pivotal importance. Thus, the aim of this article is to review the risk factors, diagnosis, and management of CDI in patients with IBD.

Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most frequently by Escherichia coli . Intestinal contiguity contributes to the etiopathogenesis of RC and an alteration in intestinal permeability could have a major role in RC. The aim of this pilot study is to assess gut microbiome dysbiosis and intestinal permeability in female patients with RC. Patients with RC ( n = 16) were enrolled and compared with healthy female subjects ( n = 15) and patients with chronic gastrointestinal (GI) disorders ( n = 238). We calculated the Acute Cystitis Symptom Score/Urinary Tract Infection Symptom Assessment (ACSS/UTISA) and Gastrointestinal Symptom Rating Scale (GSRS) scores and evaluated intestinal permeability and the fecal microbiome in the first two cohorts. Patients with RC showed an increased prevalence of gastrointestinal symptoms compared with healthy controls. Of the patients with RC, 88% showed an increased intestinal permeability with reduced biodiversity of gut microbiota compared to healthy controls, and 68% of the RC patients had a final diagnosis of gastrointestinal disease. Similarly, GI patients reported a higher incidence of urinary symptoms with a diagnosis of RC in 20%. Gut barrier impairment seems to play a major role in the pathogenesis of RC. Further studies are necessary to elucidate the role of microbiota and intestinal permeability in urinary tract infections.

To date, there is still partial data on the effects of COVID-19 on pregnant women. The constant collection of information results in a continuous updating of the knowledge about the best management of pregnant patients affected by COVID-19. This work aimed to summarize the state of the art on prevention and management of SARS-CoV-2 infection in obstetric patients. This was enabled by a comprehensive literature search for the most recent and relevant publications on the subject, including guidelines and recommendations. Management of these women by a multidisciplinary team is of crucial importance, given the extreme clinical complexity of this condition. Every health worker involved must put in place all possible procedures to protect themselves from contagion. Neuraxial anesthesia should be favored in the management of labor and caesarean section over other modalities, unless there are contraindications based on the patient's status. There is still no standardized drug treatment in pregnant women with COVID-19 due to their exclusion from studies conducted to evaluate pharmacological therapies. Nevertheless, various drugs have been used to treat this disease in pregnancy, although the data at our disposal are still few. As regards mRNA vaccines, it seems that their immunogenicity, safety and tolerability in pregnant women are comparable to those of non-pregnant women of the same age. More studies are certainly needed in infected pregnant women to establish treatment and prevention protocols for this special category of patients.

The gut microbiota is considered a key component in many aspects of cancer pathophysiology and response to therapy. In particular, in recent years intriguing evidences has been emerging regarding the role of the intestinal microbiota in the response to immunotherapy and in promoting the development of adverse events, such as colitis. For this reason, studies are being carried out both on pre-clinical models and on humans to study how to predict the response to immunotherapy through the study of the microbiota or how to improve its clinical response through modulation. Promising data have recently been reported through modulation by probiotics or prebiotics, and in particular by fecal microbiota transplantation. The aim of this review is to analyze the evidence regarding the role of the microbiota in immunotherapy with a particular focus on melanoma.

Gut microbiota is a complex ecosystem composed by trillions of microorganisms that are crucial for human health or disease status. Currently, there are two methodological options to explore its complexity: metagenomics and culturomics. Culturomics is an approach that uses multiple culture conditions (days of incubation, enrichment factors and growth temperature) and MALDI-TOF mass spectrometry for the identification of bacterial species and sequencing when this method fails. In this paper, we describe how Colturomic's protocol has allowed the first isolation in human sample of Rummeliibacillus suwonensis, a Gram positive, facultative anaerobe bacterium. The bacterium was isolated from feces of a 69 years old male with amyotrophic lateral sclerosis (ALS) recruited for a clinical trial assessing safety and efficacy of fecal microbiota transplantation in ALS. The first isolation of the microorganism dates back to 2013 from the soil of a South Korean mountain area. In this report, morphological description, biochemical characterization and antibiotic susceptibility tests were performed to outline the bacterial properties., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Spinal anesthesia (SA) is widely used for anesthetic management of patients undergoing hip surgery, and hypotension is the most common cardiovascular side effect of SA. This paper aims to assess the lowest effective dose of SA that reduces the occurrence of intraoperative hypotension in elderly patients scheduled for major lower limb orthopedic surgery., Methods: We conducted a systematic review of randomized controlled trials (RCTs) performed in elderly patients scheduled for surgical hip repair and a meta-analysis with meta-regression on the occurrence of hypotensive episodes at different effective doses of anesthetics. We searched PUBMED®, EMBASE®, and the Cochrane Controlled Clinical trials registered., Results: Our search retrieved 2085 titles, and after screening, 6 were finally included in both the qualitative and quantitative analysis, including 344 patients [15% (10-28) males], with a median (25th to 75th interquartile) age of 82 (80-85). The risk of bias assessment reported "low risk" for 5 (83.3%) and "some concerns" for 1 (16.7%) of the included RCTs. The low dose of SA of [mean 6.5 mg (1.9)] anesthetic was associated with a lower incidence of hypotension [OR = 0.09 (95%CI 0.04-0.21); p = 0.04; I 2 = 56.9%], as compared to the high-dose of anesthetic [mean 10.5 mg (2.4)]., Conclusions: In the included studies of this meta-analysis, a mean dose of 6.5 mg of SA was effective in producing intraoperative comfort and motor block and associated with a lower incidence of hypotension as compared to a mean dose of 10.5 mg., Trial Registration: CRD42020193627., (© 2022. The Author(s).)

Background: As delayed intubation may worsen the outcome of coronavirus disease 2019 (COVID-19) patients treated with continuous positive airway pressure (CPAP), we sought to determine COVID-specific early predictors of CPAP failure., Methods: In this observational retrospective multicentre study, we included all COVID-19 patients treated with out-of-ICU CPAP, candidates for intubation in case of CPAP failure. From these patients, we collected demographic and clinical data., Results: A total of 397 COVID-19 patients were treated with CPAP for respiratory failure, with the therapeutic goal of providing intubation in case of CPAP failure. Univariable analysis showed that, age, lactate dehydrogenase (LDH) and white cell counts were all significantly lower in patients with successful CPAP treatment compared to those failing it and undergoing subsequent intubation. The percentage changes between baseline and CPAP application in the ratio of partial pressure arterial oxygen (PaO 2 ) and fraction of inspired oxygen (FiO 2 ), PaO 2, respiratory rate and ROX index were higher in patients experiencing successful CPAP compared to those failing it. FiO 2 and male gender were also significantly associated with intubation. Multivariable analysis adjusting for age, gender, Charlson comorbidity index, percentage change in PaO 2 /FiO 2 or PaO 2 and FiO 2 separately, lactate, white blood cell count, LDH and C-reactive protein levels led to an area under the curve of 0.818 and confirmed that age, LDH and percentage increase in PaO 2 /FiO 2 are predictors of intubation., Conclusions: In COVID-19 patients requiring CPAP, age, LDH and percentage change in PaO 2 /FiO 2 after starting CPAP are predictors of intubation., (Copyright © 2021 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The carotid artery velocity-time integral (CVTI) and the carotid Doppler peak velocity (cDPV), as well as measures of their variation induced by the respiratory cycle, have been proposed as fast and easy to obtain ultrasound measures for assessing fluid responsiveness in intensive care unit patients. To investigate this possibility, we conducted a prospective observational study in hemodynamically unstable patients under mechanical ventilation., Methods: From May 1 to December 31, 2019, we conducted a prospective observational study involving 50 hemodynamically unstable patients under mechanical ventilation. We obtained a total of 800 Doppler ultrasound measurements from the left common carotid artery and at the level of the aortic annulus in the apical five-chamber view. The two measurements were performed before and after a 7 mL/kg fluid challenge and within the first hour of the onset of hemodynamic instability. The maximum Doppler peak velocity, the minimum Doppler peak velocity, and the maximum and minimum VTI at both the aortic and carotid level were acquired., Results: Twenty-eight (56%) patients showed a ≥15% increase in AoVTI after the fluid challenge, and were therefore identified as "fluid responders". All Doppler measurements were always significantly greater (P<0.0001) in fluid responders in relation to both carotid and aortic parameters. Good agreement between the above-mentioned measurements was found: Cohen's kappa coefficient between the carotid and aortic ΔDPV was 0.76 (95% CI 0.58-0.94); and between the Carotid and Aortic ΔVTI it was 0.84 (95% CI 0.68-0.99)., Conclusions: CDPV was found to predict fluid responsiveness in unstable mechanically ventilated patients.

The human gut microbiome (GM) is a complex ecosystem that includes numerous prokaryotic and eukaryotic inhabitants. The composition of GM can influence an array of host physiological functions including immune development. Accumulating evidence suggest that several members of non-bacterial microbiota, including protozoa and helminths, that were earlier considered as pathogens, could have a commensal or beneficial relationship with the host. Here we examine the most recent data from omics studies on prokaryota-meiofauna-host interaction as well as the impact of gut parasitome on gut bacterial ecology and its role as 'immunological driver' in health and disease to glimpse new therapeutic perspectives., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2022.)

Background: Driving pressure can be readily measured during assisted modes of ventilation such as pressure support ventilation (PSV) and neurally adjusted ventilatory assist (NAVA). The present prospective randomized crossover study aimed to assess the changes in driving pressure in response to variations in the level of assistance delivered by PSV vs NAVA., Methods: 16 intubated adult patients, recovering from hypoxemic acute respiratory failure (ARF) and undergoing assisted ventilation, were randomly subjected to six 30-min-lasting trials. At baseline, PSV (PSV100) was set with the same regulation present at patient enrollment. The corresponding level of NAVA (NAVA100) was set to match the same inspiratory peak of airway pressure obtained in PSV100. Therefore, the level of assistance was reduced and increased by 50% in both ventilatory modes (PSV50, NAVA50; PSV150, NAVA150). At the end of each trial, driving pressure obtained in response to four short (2-3 s) end-expiratory and end-inspiratory occlusions was analyzed., Results: Driving pressure at PSV50 (6.6 [6.1-7.8] cmH 2 O) was lower than that recorded at PSV100 (7.9 [7.2-9.1] cmH 2 O, P = 0.005) and PSV150 (9.9 [9.1-13.2] cmH 2 O, P < 0.0001). In NAVA, driving pressure at NAVA50 was reduced compared to NAVA150 (7.7 [5.1-8.1] cmH 2 O vs 8.3 [6.4-11.4] cmH 2 O, P = 0.013), whereas there were no changes between baseline and NAVA150 (8.5 [6.3-9.8] cmH 2 O vs 8.3 [6.4-11.4] cmH 2 O, P = 0.331, respectively). Driving pressure at PSV150 was higher than that observed in NAVA150 (P = 0.011)., Conclusions: NAVA delivers better lung-protective ventilation compared to PSV in hypoxemic ARF patients., Trial Registration Number and Date of Registration: The present trial was prospectively registered at www.clinicatrials.gov (NCT03719365) on 24 October 2018., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature.)

Background: Fluid challenge (FC) is often adopted as gold standard used to assess the reliability of passive leg raising (PLR) in predicting fluid responsiveness in the intensive care unit (ICU). This study aimed to address the impact of the different definitions and timings used to assess FC response on PLR reliability., Methods: Ancillary study from a data set of a multicentric study in 85 ICU patient with acute circulatory failure who received a FC (500 mL of crystalloids in 10 minutes) within the first 48h of ICU admission, preceded by PLR in 30 patients. FC response was assessed considering the changes in Cardiac Index (CI) and Stroke Volume Index (SVI) using different thresholds and at different time-points., Results: The definitions of fluid responsiveness by using CI or SVI with a 15% increase after 10 minutes were associated to the best performances of the PLR (AUC 0.94 [95% CI 0.83-1.01] vs. AUC 0.95 [95% CI 0.87-1.02]). The sensitivity of the PLR by adopting the CI or the SVI as reference variable ranged from 54.1% to 67.6% and from 81.5% to 100.0%; the specificity from 65.9% to 78.0% and from 79.5% to 100.0%, respectively. Considering all the subgroups, the number of responders 10 minutes after FC administration was higher as compared to 15 and 30 minutes (140 vs. 120 and 125, respectively, P<0.05)., Conclusions: The reliability of the PLR test to predict fluid responsiveness depends on the definition of FC adopted. The timing of FC outcome assessment affected the overall fluid responsiveness.

Non-invasive ventilation (NIV) has been shown to be effective in avoiding intubation and improving survival in patients with acute hypoxemic respiratory failure (ARF) when compared to conventional oxygen therapy. However, NIV is associated with high failure rates due, in most cases, to patient discomfort. Therefore, increasing attention has been paid to all those interventions aimed at enhancing patient's tolerance to NIV. Several practical aspects have been considered to improve patient adaptation. In particular, the choice of the interface and the ventilatory setting adopted for NIV play a key role in the success of respiratory assistance. Among the different NIV interfaces, tolerance is poorest for the nasal and oronasal masks, while helmet appears to be better tolerated, resulting in longer use and lower NIV failure rates. The choice of fixing system also significantly affects patient comfort due to pain and possible pressure ulcers related to the device. The ventilatory setting adopted for NIV is associated with varying degrees of patient comfort: patients are more comfortable with pressure-support ventilation (PSV) than controlled ventilation. Furthermore, the use of electrical activity of the diaphragm (EADi)-driven ventilation has been demonstrated to improve patient comfort when compared to PSV, while reducing neural drive and effort. If non-pharmacological remedies fail, sedation can be employed to improve patient's tolerance to NIV. Sedation facilitates ventilation, reduces anxiety, promotes sleep, and modulates physiological responses to stress. Judicious use of sedation may be an option to increase the chances of success in some patients at risk for intubation because of NIV intolerance consequent to pain, discomfort, claustrophobia, or agitation. During the Coronavirus Disease-19 (COVID-19) pandemic, NIV has been extensively employed to face off the massive request for ventilatory assistance. Prone positioning in non-intubated awake COVID-19 patients may improve oxygenation, reduce work of breathing, and, possibly, prevent intubation. Despite these advantages, maintaining prone position can be particularly challenging because poor comfort has been described as the main cause of prone position discontinuation. In conclusion, comfort is one of the major determinants of NIV success. All the strategies aimed to increase comfort during NIV should be pursued., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cammarota, Simonte and De Robertis.)

Background: During the COVID-19 pandemic, lung ultrasound (LUS) has been widely used since it can be performed at the patient's bedside, does not produce ionizing radiation, and is sufficiently accurate. The LUS score allows for quantifying lung involvement; however, its clinical prognostic role is still controversial., Methods: A retrospective observational study on 103 COVID-19 patients with respiratory failure that were assessed with an LUS score at intensive care unit (ICU) admission and discharge in a tertiary university COVID-19 referral center., Results: The deceased patients had a higher LUS score at admission than the survivors (25.7 vs. 23.5; p -value = 0.02; cut-off value of 25; Odds Ratio (OR) 1.1; Interquartile Range (IQR) 1.0-1.2). The predictive regression model shows that the value of LUSt0 (OR 1.1; IQR 1.0-1.3), age (OR 1.1; IQR 1.0-1.2), sex (OR 0.7; IQR 0.2-3.6), and days in spontaneous breathing (OR 0.2; IQR 0.1-0.5) predict the risk of death for COVID-19 patients (Area under the Curve (AUC) 0.92). Furthermore, the surviving patients showed a significantly lower difference between LUS scores at admission and discharge (mean difference of 1.75, p -value = 0.03)., Conclusion: Upon entry into the ICU, the LUS score may play a prognostic role in COVID-19 patients with ARDS. Furthermore, employing the LUS score as a monitoring tool allows for evaluating the patients with a higher probability of survival.

Objective: To analyze the application of lung ultrasound (LUS) diagnostic approach in obstetric patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and compare LUS score and symptoms of the patients., Design: A single-center observational retrospective study from October 31, 2020 to March 31, 2021., Setting: Department of Ob/Gyn at the University-Hospital of Udine, Italy., Participants: Pregnant women with SARS-CoV-2 diagnosed with reverse transcription-PCR (RT-PCR) swab test were subdivided as symptomatic and asymptomatic patients with COVID-19., Exposure: Lung ultrasound evaluation both through initial evaluation upon admission and through serial evaluations., Main Outcome: Reporting LUS findings and LUS score characteristics., Results: Symptomatic patients with COVID-19 showed a higher LUS (median 3.5 vs. 0, p < 0.001). LUS was significantly correlated with COVID-19 biomarkers as C-reactive protein (CPR; p = 0.011), interleukin-6 ( p = 0.013), and pro-adrenomedullin ( p = 0.02), and inversely related to arterial oxygen saturation ( p = 0.004). The most frequent ultrasound findings were focal B lines (14 vs. 2) and the light beam (9 vs. 0)., Conclusion: Lung ultrasound can help to manage pregnant women with SARS-CoV-2 infection during a pandemic surge., Study Registration: ClinicalTrials.gov, NCT04823234. Registered on March 29, 2021., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vetrugno, Sala, Orso, Meroi, Fabbro, Boero, Valent, Cammarota, Restaino, Vizzielli, Girometti, Merelli, Tascini, Bove, Driul and the PINK-CO study investigators.)

Background: The digestive tract represents an interface between the external environment and the body where the interaction of a complex polymicrobial ecology has an important influence on health and disease. The physiological mechanisms that are altered during hospitalization and in the intensive care unit (ICU) contribute to the pathobiota's growth. Intestinal dysbiosis occurs within hours of being admitted to ICU. This may be due to different factors, such as alterations of normal intestinal transit, administration of various medications, or alterations in the intestinal wall, which causes a cascade of events that will lead to the increase of nitrates and decrease of oxygen concentration, and the liberation of free radicals., Objective: This work aims to report the latest updates on the microbiota's contribution to developing sepsis in patients in the ICU department. In this short review, the latest scientific findings on the mechanisms of intestinal immune defenses performed both locally and systemically have been reviewed. Additionally, we considered it necessary to review the literature on the basis of the many studies carried out on the microbiota in the critically ill as a prevention to the spread of the infection in these patients., Materials and Methods: This review has been written to answer four main questions: 1- What are the main intestinal flora's defense mechanisms that help us to prevent the risk of developing systemic diseases? 2- What are the main Systemic Abnormalities of Dysbiosis? 3- What are the Modern Strategies Used in ICU to Prevent the Infection Spreading? 4- What is the Relationship between COVID-19 and Microbiota? We reviewed 72 articles using the combination of following keywords: "microbiota" and "microbiota" and "intensive care", "intensive care" and "gut", "critical illness", "microbiota" and "critical care", "microbiota" and "sepsis", "microbiota" and "infection", and "gastrointestinal immunity" in: Cochrane Controlled Trials Register, Cochrane Library, Medline and Pubmed, Google Scholar, Ovid/Wiley. Moreover, we also consulted the site ClinicalTrials.com to find out studies that have been recently conducted or are currently ongoing., Results: The critical illness can alter intestinal bacterial flora leading to homeostasis disequilibrium. Despite numerous mechanisms, such as epithelial cells with calciform cells that together build a mechanical barrier for pathogenic bacteria, the presence of mucous associated lymphoid tissue (MALT) which stimulates an immune response through the production of interferon-gamma (IFN-y) and THN-a or or from the production of anti-inflammatory cytokines produced by lymphocytes Thelper 2. But these defenses can be altered following hospitalization in ICU and lead to serious complications, such as acute respiratory distress syndrome (ARDS), health care associated pneumonia (HAP) and ventilator associated pneumonia (VAP), systemic infection and multiple organ failure (MOF), but also to the development of coronary artery disease (CAD). In addition, the microbiota has a significant impact on the development of intestinal complications and the severity of the SARS-COVID-19 patients., Conclusion: The microbiota is recognized as one of the important factors that can worsen the clinical conditions of patients who are already very frail in the intensive care unit. At the same time, the microbiota also plays a crucial role in the prevention of ICU-associated complications. By using the resources that are available, such as probiotics, synbiotics or fecal microbiota transplantation (FMT), we can preserve the integrity of the microbiota and the GUT, which will later help maintain homeostasis in ICU patients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Aims: Many studies have shown a high effectiveness of fecal microbiota transplantation (FMT) in treatment of recurrent or refractory Clostridioides difficile infection (CDI). Nevertheless, data on long term outcomes and complications after FMT are still lacking. We aimed to evaluate the efficacy, the peri- procedural safety profile and the long-term efficacy and safety of FMT for recurrent CDI during a median follow up period of 24 months., Methods: Our study included 60 consecutive patients that were treated from 2015 to 2019 for recurrent CDI. In all patients FMT was performed through the nasoenteric tube placed during gastroscopy. Fresh donor feces were used for FMT from unrelated donors. Pre-FMT preparation included CDI treatment with oral vancomycin 500 mg q.i.d. for at least five days and proton pump inhibitor (PPI) administration before FMT. Follow up data included information about recurrent CDI episodes, early and late complications, health status at 3, 12 and 24 months after FMT., Results: FMT was performed for 60 patients (median age 72.5 years) with recurrent CDI. Clinical improvement after the first FMT procedure was observed in 48 patients (80%). Ten of 12 initially non-responding patients had a clinical resolution after a second FMT leading to an increased overall cure rate of 96.7 %. The remaining two patients needed a third FMT with a final overall cure rate of 100%. Nine of 60 patients were under immunosuppressive therapy. Six immunosuppressed patients were in the group of initial responders and the remaining three in the initially non-responder group. We observed a very low rate of adverse events in the short and long-term after FMT. During the first eight weeks after the FMT procedure, the death of three patients occurred, but they were not related to the FMT procedure. Patients were followed up for a median of 20 months, with the range from 12 to 55 months. During the follow-up period no long-term serious adverse events (SAE) were documented., Conclusions: Our study confirms excellent efficacy rates of FMT in the treatment of recurrent CDI. In addition, this study shows that it is possible to avoid short term SAE when FMT is administered via a nasoenteric tube by following a very stringent peri-procedural patient follow-up protocol. Our study also demonstrates good safety with a low rate of long-term adverse events after FMT.

Background: Estimating the risk of intubation and mortality among COVID-19 patients can help clinicians triage these patients and allocate resources more efficiently. Thus, here we sought to identify the risk factors associated with intubation and intra-hospital mortality in a cohort of COVID-19 patients hospitalized due to hypoxemic acute respiratory failure (ARF)., Results: We included retrospectively a total of 187 patients admitted to the subintensive and intensive care units of the University Hospital "Maggiore della Carità" of Novara between March 1st and April 30th, 2020. Based on these patients' demographic characteristics, early clinical and laboratory variables, and quantitative chest computerized tomography (CT) findings, we developed two random forest (RF) models able to predict intubation and intra-hospital mortality. Variables independently associated with intubation were C-reactive protein (p < 0.001), lactate dehydrogenase level (p = 0.018) and white blood cell count (p = 0.026), while variables independently associated with mortality were age (p < 0.001), other cardiovascular diseases (p = 0.029), C-reactive protein (p = 0.002), lactate dehydrogenase level (p = 0.018), and invasive mechanical ventilation (p = 0.001). On quantitative chest CT analysis, ground glass opacity, consolidation, and fibrosis resulted significantly associated with patient intubation and mortality. The major predictors for both models were the ratio between partial pressure of arterial oxygen and fraction of inspired oxygen, age, lactate dehydrogenase, C-reactive protein, glycemia, CT quantitative parameters, lymphocyte count, and symptom onset., Conclusions: Altogether, our findings confirm previously reported demographic, clinical, hemato-chemical, and radiologic predictors of adverse outcome among COVID-19-associated hypoxemic ARF patients. The two newly developed RF models herein described show an overall good level of accuracy in predicting intra-hospital mortality and intubation in our study population. Thus, their future development and implementation may help not only identify patients at higher risk of deterioration more effectively but also rebalance the disproportion between resources and demand., (© 2021. The Author(s).)

Background: To produce statements based on the available evidence and an expert consensus (as members of the Lung Ultrasound Working Group of the Italian Society of Analgesia, Anesthesia, Resuscitation, and Intensive Care, SIAARTI) on the use of lung ultrasound for the management of patients with COVID-19 admitted to the intensive care unit., Methods: A modified Delphi method was applied by a panel of anesthesiologists and intensive care physicians expert in the use of lung ultrasound in COVID-19 intensive critically ill patients to reach a consensus on ten clinical questions concerning the role of lung ultrasound in the following: COVID-19 diagnosis and monitoring (with and without invasive mechanical ventilation), positive end expiratory pressure titration, the use of prone position, the early diagnosis of pneumothorax- or ventilator-associated pneumonia, the process of weaning from invasive mechanical ventilation, and the need for radiologic chest imaging., Results: A total of 20 statements were produced by the panel. Agreement was reached on 18 out of 20 statements (scoring 7-9; "appropriate") in the first round of voting, while 2 statements required a second round for agreement to be reached. At the end of the two Delphi rounds, the median score for the 20 statements was 8.5 [IQR 8.9], and the agreement percentage was 100%., Conclusion: The Lung Ultrasound Working Group of the Italian Society of Analgesia, Anesthesia, Resuscitation, and Intensive Care produced 20 consensus statements on the use of lung ultrasound in COVID-19 patients admitted to the ICU. This expert consensus strongly suggests integrating lung ultrasound findings in the clinical management of critically ill COVID-19 patients., (© 2021. The Author(s).)

In December 2019 a novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), started spreading from Wuhan city of Chinese Hubei province and rapidly became a global pandemic. Clinical symptoms of the disease range from paucisymptomatic disease to a much more severe disease. Typical symptoms of the initial phase include fever and cough, with possible progression to acute respiratory distress syndrome. Gastrointestinal manifestations such as diarrhoea, vomiting and abdominal pain are reported in a considerable number of affected individuals and may be due to the SARS-CoV-2 tropism for the peptidase angiotensin receptor 2. The intestinal homeostasis and microenvironment appear to play a major role in the pathogenesis of COVID-19 and in the enhancement of the systemic inflammatory responses. Long-term consequences of COVID-19 include respiratory disturbances and other disabling manifestations, such as fatigue and psychological impairment. To date, there is a paucity of data on the gastrointestinal sequelae of SARS-CoV-2 infection. Since COVID-19 can directly or indirectly affect the gut physiology in different ways, it is plausible that functional bowel diseases may occur after the recovery because of potential pathophysiological alterations (dysbiosis, disruption of the intestinal barrier, mucosal microinflammation, post-infectious states, immune dysregulation and psychological stress). In this review we speculate that COVID-19 can trigger irritable bowel syndrome and we discuss the potential mechanisms., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interests., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)