Peri-partum respiratory management of pregnant women with neuro-muscular disorders: a prospective observational study (IT-NEUMA-Pregn study).

BACKGROUND: Pregnant women with neuromuscular diseases (NMDs) often display respiratory muscle impairment which increases the risk for pulmonary complications (PCs). The aim of this study was to identify pregnant NMDs patients with pulmonary risk factors and to apply in these women non-invasive ventilation (NIV) combined with mechanical insufflation-exsufflation (MI-E) in the peri-partum period. METHODS: We conducted a multicenter observational study on women with NMDs undergoing cesarean section or spontaneous labor in a network of 7 national hospitals. In these subjects we applied a protocol for screening and preventing PCs, and we evaluated PCs rate, maternal and neonatal outcome. RESULTS: Twenty-four patients out of the 94 enrolled pregnant women were at risk for PCs and were trained or retrained to use NIV and/or MI-E before delivery. After delivery, 17 patients required NIV with or without MI-E. Despite nine out of the 24 women at pulmonary risk developed postpartum PCs, none of them needed reintubation nor tracheostomy. In addition, the average birth weight and Apgar score were normal. Only one patient without pulmonary risk factors developed postpartum PCs. CONCLUSION: This study showed the feasibility of applying a protocol for screening and treating pregnant NMDs women with pulmonary risk. Despite a PCs rate of 37% was observed in these patients, maternal and neonatal outcome were favorable.

Severe Trauma-Induced Coagulopathy: Molecular Mechanisms Underlying Critical Illness.

Trauma remains one of the leading causes of death in adults despite the implementation of preventive measures and innovations in trauma systems. The etiology of coagulopathy in trauma patients is multifactorial and related to the kind of injury and nature of resuscitation. Trauma-induced coagulopathy (TIC) is a biochemical response involving dysregulated coagulation, altered fibrinolysis, systemic endothelial dysfunction, platelet dysfunction, and inflammatory responses due to trauma. The aim of this review is to report the pathophysiology, early diagnosis and treatment of TIC. A literature search was performed using different databases to identify relevant studies in indexed scientific journals. We reviewed the main pathophysiological mechanisms involved in the early development of TIC. Diagnostic methods have also been reported which allow early targeted therapy with pharmaceutical hemostatic agents such as TEG-based goal-directed resuscitation and fibrinolysis management. TIC is a result of a complex interaction between different pathophysiological processes. New evidence in the field of trauma immunology can, in part, help explain the intricacy of the processes that occur after trauma. However, although our knowledge of TIC has grown, improving outcomes for trauma patients, many questions still need to be answered by ongoing studies.

Cytokine Storm in COVID-19: Immunopathogenesis and Therapy.

A cytokine storm is a hyperinflammatory state secondary to the excessive production of cytokines by a deregulated immune system. It manifests clinically as an influenza-like syndrome, which can be complicated by multi-organ failure and coagulopathy, leading, in the most severe cases, even to death. The term cytokine storm was first used in 1993 to describe the graft-versus-host disease following allogeneic hematopoietic stem cell transplantation. It was then reused to define the adverse syndromes secondary to the administration of immunostimulating agents, such as anti-CD28 antibodies or bioengineered immune cells, i.e., CAR T-cell therapy. Currently, the concept of cytokine storm has been better elucidated and extended to the pathogenesis of many other conditions, such as sepsis, autoinflammatory disease, primary and secondary hemophagocytic lymphohistiocytosis, and multicentric Castleman disease. Moreover, cytokine storm has recently emerged as a key aspect in the novel Coronavirus disease 2019, as affected patients show high levels of several key pro-inflammatory cytokines, such as IL-1, IL-2, IL-6, TNF-α, IFN-γ, IP-10, GM-CSF, MCP-1, and IL-10, some of which also correlate with disease severity. Therefore, since the onset of the pandemic, numerous agents have been tested in the effort to mitigate the cytokine storm in COVID-19 patients, some of which are effective in reducing mortality, especially in critically ill patients, and are now becoming standards of care, such as glucocorticoids or some cytokine inhibitors. However, the challenge is still far from being met, and other therapeutic strategies are being tested in the hope that we can eventually overcome the disease.

Probiotic Bacterial Application in Pediatric Critical Illness as Coadjuvants of Therapy.

The use of probiotics in critically ill adult and children patients has been growing exponentially over the last 20 years. Numerous factors in pediatriac intensive care unit (PICU) patients may contribute to intestinal dysbiosis, which subsequently promotes the pathobiota's growth. Currently, lactobacillus and bifidobacterium species are mainly used to prevent the development of systemic diseases due to the subverted microbiome, followed by streptococcus, enterococcus, propionibacterium, bacillus and Escherichia coli, Lactobacillus rhamnosus GG, and Lactobacillus reuteri DSM 17938. The aim of this article is to review the scientific literature for further confirmation of the importance of the usage of probiotics in intensive care unit (ICU) patients, especially in the pediatric population. A progressive increase in nosocomial infections, especially nosocomial bloodstream infections, has been observed over the last 30 years. The World Health Organization (WHO) reported that the incidence of nosocomial infections in PICUs was still high and ranged between 5% and 10%. Petrof et al. was one of the first to demonstrate the efficacy of probiotics for preventing systemic diseases in ICU patients. Recently, however, the use of probiotics with different lactobacillus spp. has been shown to cause a decrease of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines. In addition, in some studies, the use of probiotics, in particular the mix of Lactobacillus and Bifidobacterium reduces the incidence of ventilator-associated pneumonia (VAP) in PICU patients requiring mechanical ventilation. In abdominal infections, there is no doubt at all about the usefulness of using Lactobacillus spp probiotics, which help to treat ICU-acquired diarrhoea episodes as well as in positive blood culture for candida spp. Despite the importance of using probiotics being supported by various studies, their use is not yet part of the standard protocols to which all doctors must adhere. In the meantime, while waiting for protocols to be drawn up as soon as possible for use in PICUs, routine use could certainly stimulate the intestine's immune defences. Though it is still too early to say, they could be considered the drugs of the future.

Extra-Corporeal Membrane Oxygenation in Pregnancy.

Extracorporeal membrane oxygenation (ECMO) is a cardiac or pulmonary function support system that is used in cases of refractory organ failure in addition to conventional treatment. Currently, Level I evidence is not yet available, which reflects improved outcomes with ECMO in pregnant women, the use in pregnancy should be indicated in selected cases and only in specialized centers. We searched articles in the most important scientific databases from 2009 until 31 December 2023 consulting also the site ClinicalTrials.com to find out about studies that have been recently conducted or are currently ongoing. We matched the combination of the following keywords: "ECMO and pregnancy", "H1N1 and pregnancy", "COVID-19 and pregnancy", "ARDS and pregnancy", "ECMO and pregnancy AND (cardiac arrest)". We selected the following number of articles for each keyword combination: "ECMO and pregnancy" (665 articles); "ECMO and influenza H1N1" (384 articles); "pregnancy and influenza H1N1" (1006 articles); "pregnancy and ARDS" (2930 articles); "ECMO and pregnancy and ARDS and influenza H1N1" (24 articles); and "[ECMO and pregnancy AND (cardiac arrest)]" (74 articles). After careful inspection, only 43 papers fitted our scope. There are two types of ECMO: venous-venous (VV-ECMO) and venous-arterial (VA-ECMO). The first-one is necessary to cope with severe hypoxia: oxygen-depleted blood is taken from the venous circulation, oxygenated, and carbon dioxide removed from the extracorporeal circuit and returned to the same venous system. The VA-ECMO is a type of mechanical assistance to the circulatory system that allows to put the failing organ at rest by ensuring adequate oxygenation and systemic de-oxygenation, avoiding multi-organ failure. The main indications for ECMO support in pregnant women are cardiogenic shock, acute respiratory distress syndrome (ARDS), pulmonary embolism, and eclampsia. There are also fetal indications for ECMO, and they are fetal distress, hypoxic-ischemic encephalopathy (HIE), and twin-to-twin transfusion syndrome (TTTS). Until now, based on the outcomes of the numerous clinical studies conducted, ECMO has been shown to be a successful therapeutic strategy in cases where medical treatment has been unsuccessful. In well-selected pregnant patients, it appears to be safe and associated with a low risk of maternal and fetal complications. The aim of this review is to report the main properties of ECMO (VV and VA) and the indications for its use in pregnant women.

Cerebral Vasospasm: Practical Review of Diagnosis and Management.

BACKGROUND: Cerebral vasospasm is one of the frequent complications that can occur following subarachnoid hemorrhage (SAH). With new protocols in the management of SAH, the combined risk of death and long-term disability have been reduced by about 10% compared with the past. OBJECTIVE: This work aims to report the latest updates on the vasospasm developing after the SAH in patients in the ICU department. In this short review, we reviewed the latest scientific findings on the mechanisms of vasospasm, and in addition, we considered it necessary to review the literature to report the tools for early diagnosis of vasospasm and the best treatment strategies to prevent the negative outcome in patients admitted to ICU. AIM: The aim of this narrative review is to report the main characteristics of vasospasm, new diagnostic methods, and, especially, more effective treatment of vasospasm. MATERIALS AND METHODS: The peer-reviewed articles analyzed were selected from PubMed, Google scholar, Embase, and Scopus databases published in the previous 20 years using the keywords "vasospasm", "vasospasm diagnosis", "vasospasm and SAH", "vasospasm treatment", and nontraumatic brain injury. Among the 78 papers identified, 43 articles were selected; after the title - abstract examination and removing the duplicates, only 31 articles were examined. RESULTS: Vasospasm can be classified according to clinical (asymptomatic vs. symptomatic) and diagnostic (angiographic vs. ultrasound) methods. Various procedures such as TCD and CT perfusion are used for early diagnosis and close monitoring of this condition. The treatment of vasospasm consists of both prevention (nimodipine, statitis, and magnesium sulphate) and active treatment (mainly endovascular). CONCLUSION: As the review shows, vasospasm is a complication of SAH, a complication that is difficult to recognize early and treat with the best outcome. However, with the equipment we have, it has been possible to improve the outcome, even if it is still not ideal, in patients who develop vasospasm. Several studies are in the final stages to improve the outcome of this unfortunately frequent condition.

External Ventricular Drainage: A Practical Guide for Neuro-Anesthesiologists.

External ventricular drainage is often considered a life-saving treatment in acute hydrocephalus. Given the large number of discussion points, the ideal management of EVD has not been completely clarified. The objective of this study was to review the most relevant scientific evidence about the management of EVD in its main clinical scenarios. We reviewed the most recent and relevant articles about indications, timing, management, and complications of EVD in neurocritical care, with particular interest in patients with subarachnoid hemorrhage (SAH), severe traumatic brain injury (TBI), and intraventricular hemorrhage (IVH) using the following keywords alone or matching with one another: intracranial pressure, subarachnoid hemorrhage, traumatic brain injury, intraventricular hemorrhage, external ventricular drainage, cerebrospinal shunt, intracranial pressure monitoring, and ventriculoperitoneal shunt. In the management of EVD in SAH, the intermittent drainage strategy is burdened with an elevated risk of complications (e.g., clogged catheter, hemorrhage, and need for replacement). There seems to be more ventriculoperitoneal shunt dependency in rapid weaning approach-managed patients than in those treated with the gradual weaning approach. Although there is no evidence in favor of either strategy, it is conventionally accepted to adopt a continuous drainage approach in TBI patients. Less scientific evidence is available in the literature regarding the management of EVD in patients with severe TBI and intraparenchymal/intraventricular hemorrhage. EVD placement is a necessary treatment in several clinical scenarios. However, further randomized clinical trials are needed to clarify precisely how EVD should be managed in different clinical scenarios.

Decompressive Craniectomy in Severe Traumatic Brain Injury: The Intensivist's Point of View.

INTRODUCTION: Traumatic brain injury (TBI) represents a severe pathology with important social and economic concerns, decompressive craniectomy (DC) represents a life-saving surgical option to treat elevated intracranial hypertension (ICP). The rationale underlying DC is to remove part of the cranial bones and open the dura mater to create space, avoiding secondary parenchymal damage and brain herniations. The scope of this narrative review is to summarize the most relevant literature and to discuss main issues about indication, timing, surgical procedure, outcome, and complications in adult patients involved in severe traumatic brain injury, underwent to the DC. The literature research is made with Medical Subject Headings (MeSH) terms on PubMed/MEDLINE from 2003 to 2022 and we reviewed the most recent and relevant articles using the following keywords alone or matched with each other: decompressive craniectomy; traumatic brain injury; intracranial hypertension; acute subdural hematoma; cranioplasty; cerebral herniation, neuro-critical care, neuro-anesthesiology. The pathogenesis of TBI involves both primary injuries that correlate directly to the external impact of the brain and skull, and secondary injuries due to molecular, chemical, and inflammatory cascade inducing further cerebral damage. The DC can be classified into primary, defined as bone flap removing without its replacement for the treatment of intracerebral mass, and secondary, which indicates for the treatment of elevated intracranial pressure (ICP), refractory to intensive medical management. Briefly, the increased brain compliance following bone removal reflects on CBF and autoregulation inducing an alteration in CSF dynamics and so, eventual complications. The risk of complications is estimated around 40%. The main cause of mortality in DC patients is due to brain swelling. In traumatic brain injury, primary or secondary decompressive craniectomy is a life-saving surgery, and the right indication should be mandatory in multidisciplinary medical-surgical consultation.

Invasive Mechanical Ventilation in Traumatic Brain Injured Patients with Acute Respiratory Failure.

Patients with severe traumatic brain injury (TBI) need to be admitted to intensive care (ICU) because they require invasive mechanical ventilation (IMV) due to reduced consciousness resulting in loss of protective airway reflexes, reduced ability to cough and altered breathing control. In addition, these patients can be complicated by pneumonia and acute distress syndrome (ARDS). IMV allows these patients to be sedated, decreasing intracranial pressure and ensuring an adequate oxygen delivery and tight control of arterial carbon dioxide tension. However, IMV can also cause dangerous effects on the brain due to its interaction with intrathoracic and intracranial compartments. Moreover, when TBI is complicated by ARDS, the setting of mechanical ventilation can be very difficult as ventilator goals are often different and in conflict with each other. Consequently, close brain and respiratory monitoring is essential to reduce morbidity and mortality in mechanically ventilated patients with severe TBI and ARDS. Recently, recommendations for the setting of mechanical ventilation in patients with acute brain injury (ABI) were issued by the European Society of Intensive Care Medicine (ESICM). However, there is insufficient evidence regarding ventilation strategies for patients with ARDS associated with ABI. The purpose of this paper is to analyze in detail respiratory strategies and targets in patients with TBI associated with ARDS.

Lung Ultrasound in Critical Care and Emergency Medicine: Clinical Review.

Lung ultrasound has become a part of the daily examination of physicians working in intensive, sub-intensive, and general medical wards. The easy access to hand-held ultrasound machines in wards where they were not available in the past facilitated the widespread use of ultrasound, both for clinical examination and as a guide to procedures; among point-of-care ultrasound techniques, the lung ultrasound saw the greatest spread in the last decade. The COVID-19 pandemic has given a boost to the use of ultrasound since it allows to obtain a wide range of clinical information with a bedside, not harmful, repeatable examination that is reliable. This led to the remarkable growth of publications on lung ultrasounds. The first part of this narrative review aims to discuss basic aspects of lung ultrasounds, from the machine setting, probe choice, and standard examination to signs and semiotics for qualitative and quantitative lung ultrasound interpretation. The second part focuses on how to use lung ultrasound to answer specific clinical questions in critical care units and in emergency departments.

Acute Traumatic Pain in the Emergency Department.

Trauma is a major cause of mortality throughout the world. Traumatic pain-acute, sudden, or chronic-is defined as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage". Patients' perceptions of pain assessment and management have become an important criterion and relevant outcome measure for healthcare institutions. Several studies show that 60-70% of ER patients experience pain, and more than half of them express a feeling of sorrow, which can be moderate or severe, at triage. The few studies that have analyzed how pain is assessed and managed in these departments agree that approximately 70% of patients receive no analgesia or receive it with remarkable delay. Specifically, less than half of the patients receive treatment for pain during admission and 60% of discharged patients have higher intensity pain than at admission. Trauma patients are also the ones who most commonly report low satisfaction with pain management. Associated with this lack of satisfaction, we can describe the poor use of tools for measuring and recording pain, poor communication among caregivers, inadequate training in pain assessment and management, and widespread misconceptions among nurses about the reliability of patients' estimation of pain. The aim of this article is to review the scientific literature to explore the methodologies of pain management in trauma patients attending the emergency room and analyzing their weaknesses as a starting point to improve the approach to this, unfortunately too often, underestimated issue. A literature search was performed using the major databases to identify relevant studies in indexed scientific journals. The literature showed that the multimodal approach in trauma patients is the best approach to pain management. It is becoming increasingly crucial to manage the patient on multiple fronts. Drugs acting on different pathways can be administered together at lower doses, minimizing risks. Every emergency department must have staff trained in the assessment and immediate management of pain symptoms as this allows the reduction of mortality and morbidity and shortens hospital stays, contributing to early mobilization, reduced hospital costs, and enhanced patient satisfaction and quality of life.

Cardiogenic Pulmonary Edema in Emergency Medicine.

Cardiogenic pulmonary edema (CPE) is characterized by the development of acute respiratory failure associated with the accumulation of fluid in the lung's alveolar spaces due to an elevated cardiac filling pressure. All cardiac diseases, characterized by an increasing pressure in the left side of the heart, can cause CPE. High capillary pressure for an extended period can also cause barrier disruption, which implies increased permeability and fluid transfer into the alveoli, leading to edema and atelectasis. The breakdown of the alveolar-epithelial barrier is a consequence of multiple factors that include dysregulated inflammation, intense leukocyte infiltration, activation of procoagulant processes, cell death, and mechanical stretch. Reactive oxygen and nitrogen species (RONS) can modify or damage ion channels, such as epithelial sodium channels, which alters fluid balance. Some studies claim that these patients may have higher levels of surfactant protein B in the bloodstream. The correct approach to patients with CPE should include a detailed medical history and a physical examination to evaluate signs and symptoms of CPE as well as potential causes. Second-level diagnostic tests, such as pulmonary ultrasound, natriuretic peptide level, chest radiograph, and echocardiogram, should occur in the meantime. The identification of the specific CPE phenotype is essential to set the most appropriate therapy for these patients. Non-invasive ventilation (NIV) should be considered early in the treatment of this disease. Diuretics and vasodilators are used for pulmonary congestion. Hypoperfusion requires treatment with inotropes and occasionally vasopressors. Patients with persistent symptoms and diuretic resistance might benefit from additional approaches (i.e., beta-agonists and pentoxifylline). This paper reviews the pathophysiology, clinical presentation, and management of CPE.

Microbiome in Critical Care: An Unconventional and Unknown Ally.

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.

Practical Review of Mechanical Ventilation in Adults and Children in the Operating Room and Emergency Department.

BACKGROUND: During general anesthesia, mechanical ventilation can cause pulmonary damage through mechanism of ventilator-induced lung injury, which is a major cause of post-operative pulmonary complications, which varies between 5 and 33% and increases the 30-day mortality of the surgical patient significantly. OBJECTIVE: The aim of this review is to analyze different variables which played a key role in the safe application of mechanical ventilation in the operating room and emergency setting. METHODS: Also, we wanted to analyze different types of the population that underwent intraoperative mechanical ventilation like obese patients, pediatric and adult population and different strategies such as one lung ventilation and ventilation in trendelemburg position. The peer-reviewed articles analyzed were selected according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) from Pubmed/Medline, Ovid/Wiley and Cochrane Library, combining key terms such as: "pulmonary post-operative complications", "protective ventilation", "alveolar recruitment maneuvers", "respiratory compliance", "intraoperative paediatric ventilation", "best peep", "types of ventilation". Among the 230 papers identified, 150 articles were selected, after title - abstract examination and removing the duplicates, resulting in 94 articles related to mechanical ventilation in operating room and emergency setting that were analyzed. RESULTS: Careful preoperative patient's evaluation and protective ventilation (i.e., use of low tidal volumes, adequate PEEP and alveolar recruitment maneuvers) has been shown to be effective not only in limiting alveolar de-recruitment, alveolar overdistension and lung damage, but also in reducing the onset of Pulmonary Post-operative Complications (PPCs). CONCLUSION: Mechanical ventilation is like "Janus Bi-front" because it is essential for surgical procedures, for the care of critical care patients and in life-threatening conditions, but it can be harmful to the patient if continued for a long time and where an excessive dose of oxygen is administered into the lungs. Low tidal volume is associated with a minor rate of PPCs and other complications and every complication can increase the length of Stay, adding cost to NHS between 1580 € and 1650 € per day in Europe and currently the prevention of PPCS is the only weapon that we possess.

Cellular Immuno-Profile in Septic Human Host: A Scoping Review.

Innate and adaptive immune system cells play a critical role in the host response to sepsis. Sepsis is a life-threatening disease characterized by apoptosis-induced depletion of immune cells and immunodepression, which contribute to morbidity and mortality. Many alterations in the expression of surface markers of neutrophils and monocytes have been described in septic patients. The aim of this study was to inspect the recently published literature to inform the clinician about the most up-to-date techniques for the study of circulating leukocytes. The impact on cell phenotypes and on the function of leukocytes of extracorporeal and non-blood purification treatments proposed for sepsis were also analyzed. We conducted a systematic review using Pubmed/Medline, Ovid/Willey, the Cochrane Library, the Cochrane Controlled Trials Register, and EMBASE, combining key terms related to immunological function in sepsis and selected the most relevant clinical trials and review articles (excluding case reports) published in the last 50 years. The most important alteration in neutrophils during sepsis is that they activate an anti-apoptotic survival program. In septic monocytes, a reduced characteristic expression of HLA-DR is observed, but their role does not seem to be significantly altered in sepsis. As regards adaptive immunity, sepsis leads to lymphopenia and immunosuppression in patients with septic shock; this process involves all types of T cells (CD4, CD8 and Natural Killer), except for regulatory T cells, which retain their function. Several promising therapies that target the host immune response are currently under evaluation. During the worldwide pandemic caused by SARS-CoV-2, it was useful to study the "cytokine storm" to find additional treatments, such as the oXiris® filter. This therapy can decrease the concentration of inflammatory markers that affect the severity of the disease.

Ketamine in Acute Brain Injury: Current Opinion Following Cerebral Circulation and Electrical Activity.

The use of ketamine in patients with TBI has often been argued due to its possible deleterious effects on cerebral circulation and perfusion. Early studies suggested that ketamine could increase intracranial pressure, decreasing cerebral perfusion pressure and thereby reducing oxygen supply to the damaged cerebral cortex. Some recent studies have refuted these conclusions relating to the role of ketamine, especially in patients with TBI, showing that ketamine should be the first-choice drug in this type of patient at induction. Our narrative review collects evidence on ketamine's use in patients with TBI. Databases were examined for studies in which ketamine had been used in acute traumatic brain injury (TBI). The outcomes considered in this narrative review were: mortality of patients with TBI; impact on intracranial pressure and cerebral perfusion pressure; blood pressure and heart rate values; depolarization rate; and preserved neurological functions. 11 recent studies passed inclusion and exclusion criteria and were included in this review. Despite all the benefits reported in the literature, the use of ketamine in patients with brain injury still appears to be limited. A slight increase in intracranial pressure was found in only two studies, while two smaller studies showed a reduction in intracranial pressure after ketamine administration. There was no evidence of harm from the ketamine's use in patients with TBI.

Single-Breath Counting Test Predicts Non-Invasive Respiratory Support Requirements in Patients with COVID-19 Pneumonia.

The use of non-invasive respiratory strategies (NIRS) is crucial to improve oxygenation in COVID-19 patients with hypoxemia refractory to conventional oxygen therapy. However, the absence of respiratory symptoms may delay the start of NIRS. The aim of this study was to determine whether a simple bedside test such as single-breath counting test (SBCT) can predict the need for NIRS in the 24 h following the access to Emergency Department (ED). We performed a prospective observational study on 120 patients with COVID-19 pneumonia. ROC curves were used to analyze factors which might predict NIRS requirement. We found that 36% of patients had normal respiratory rate and did not experience dyspnea at rest. 65% of study population required NIRS in the 24 h following the access to ED. NIRS-requiring group presented lower PaO2/FiO2 (235.09 vs. 299.02), SpO2/FiO2 ratio (357.83 vs. 431.07), PaCO2 (35.12 vs. 40.08), and SBCT (24.46 vs. 30.36) and showed higher incidence of dyspnea at rest (57.7% vs. 28.6%). Furthermore, SBCT predicted NIRS requirement even in the subgroup of patients without respiratory symptoms (AUC = 0.882, cut-off = 30). SBCT might be a valuable tool for bedside assessment of respiratory function in patients with COVID-19 pneumonia and might be considered as an early clinical sign of impending respiratory deterioration.

Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019.

Since the end of 2019, the medical-scientific community has been facing a terrible pandemic caused by a new airborne viral agent known as SARS-CoV2. Already in the early stages of the pandemic, following the discovery that the virus uses the ACE2 cell receptor as a molecular target to infect the cells of our body, it was hypothesized that the renin-angiotensin-aldosterone system was involved in the pathogenesis of the disease. Since then, numerous studies have been published on the subject, but the exact role of the renin-angiotensin-aldosterone system in the pathogenesis of COVID-19 is still a matter of debate. RAAS represents an important protagonist in the pathogenesis of COVID-19, providing the virus with the receptor of entry into host cells and determining its organotropism. Furthermore, following infection, the virus is able to cause an increase in plasma ACE2 activity, compromising the normal function of the RAAS. This dysfunction could contribute to the establishment of the thrombo-inflammatory state characteristic of severe forms of COVID-19. Drugs targeting RAAS represent promising therapeutic options for COVID-19 sufferers.