The myth of septic complications of acute pneumonia

A new era in the treatment of acute pneumonia (AP) began with the introduction of antibiotics into medical practice. The first successes of the use of new drugs were accompanied by a gradual simplification of views on the nature of AP with an emphasis on the characteristics of the pathogen and its suppression. A huge layer of scientific materials that allow us to understand the features of the development and course of inflammatory processes in the lungs, remained unclaimed. The focus on the etiology of the disease has led to a distorted view of its mechanisms and an exaggerated diagnosis of septic complications that do not have a reasoned confirmation. The current pandemic with a large number of COVID-19 pneumonias has radically changed the etiology of AP and deprived practical medicine of conventional treatment regimens. The unpreparedness of modern medicine for such a challenge and the preservation of the previous ideology of the disease are the reason for a radical revision of the AP doctrine. © 2020 The author (s).

Diagnostic des pneumonies aiguës communautaires aux urgences et distinction entre étiologie virale ou bactérienne

La pandémie actuelle liée à l'émergence du SARSCoV-2 en 2019 a considérablement modifié la perception des médecins de l'impact des virus respiratoires et de leur rôle dans les pneumonies aiguës communautaires (PAC). Alors que plus de 25 % des tableaux de PAC chez l'adulte étaient d'origine virale, les virus respiratoires étaient souvent perçus comme des agents pathogènes peu graves. Devant le défi que représente encore à nos jours la documentation microbiologique d'une PAC, l'instauration d'un traitement empirique par antibiotiques est souvent réalisée aux urgences. La pandémie de COVID-19 a surtout mis en exergue le rôle déterminant de la biologie moléculaire et du scanner thoracique dans l'algorithme diagnostique de la PAC. En effet, un diagnostic rapide et fiable est la clé pour améliorer les mesures de précaution et réduire la prescription inutile d'antibiotiques. Du fait de prises en charges très différentes, il est nécessaire de distinguer l'étiologie virale de la bactérienne d'une PAC.Alternate : The current pandemic linked to the emergence of SARS-CoV-2 in 2019 has considerably changed the perception of doctors of the impact of respiratory viruses and their role in community-acquired acute pneumonia (CAP). While more than 25% of CAP in adults were of viral origin, respiratory viruses were often perceived as harmless pathogens. Faced with the challenge that the microbiological documentation of a CAP still represents today, the establishment of empirical antibiotic treatment is often carried out in the emergency room. The COVID-19 pandemic has primarily highlighted the decisive role of molecular biology and chest CT in the diagnostic algorithm of CAP. Indeed, a rapid and reliable diagnosis is the key to improve isolation decisions and reducing the unnecessary prescription of antibiotics. Due to significantly different treatments, it is necessary to distinguish the viral etiology from the bacterial of a CAP.

Diagnosis of community-acquired acute pneumonia in the emergency room and distinction between viral or bacterial etiology.

The current pandemic linked to the emergence of SARS-CoV-2 in 2019 has considerably changed the perception of doctors of the impact of respiratory viruses and their role in community-acquired acute pneumonia (CAP). While more than 25% of CAP in adults were of viral origin, respiratory viruses were often perceived as harmless pathogens. Faced with the challenge that the microbiological documentation of a CAP still represents today, the establishment of empirical antibiotic treatment is often carried out in the emergency room. The COVID-19 pandemic has primarily highlighted the decisive role of molecular biology and chest CT in the diagnostic algorithm of CAP. Indeed, a rapid and reliable diagnosis is the key to improve isolation decisions and reducing the unnecessary prescription of antibiotics. Due to significantly different treatments, it is necessary to distinguish the viral etiology from the bacterial of a CAP. Copyright © 2022 Lavoisier. All rights reserved.

Aloe polymeric acemannan inhibits the cytokine storm in mouse pneumonia models by modulating macrophage metabolism.

The cytokine storm is highly associated with inflammatory-type disease severity and patients' survival. Plant polysaccharides, the main natural phytomedicine source, have a great potential to be an effective drug to treat cytokine storm. Herein we found that a polymeric acemannan (ABPA1) isolated from Aloe Vera Barbadensis extract C (AVBEC) exerted prominent inhibitory effects on inflammation-induced cytokine storm. The results displayed that ABPA1 effectively suppressed LPS-induced proinflammatory cytokines release in vitro. Moreover, ABPA1 treatment alleviated the cytokine storm and tissue damage in LPS- and IAV-induced mouse pneumonia models, and altered the phenotypic balance of macrophages in lung tissues. Functionally, ABPA1 enhanced macrophage M2 polarization and phagocytosis in RAW264.7 cells and inhibited LPS-induced M1 polarization. Mechanistically, ABPA1 enhanced mitochondrial metabolism and OXPHOS through activated PI3K/Akt/GSK-3ß signalling pathway. Overall, our findings suggest that ABPA1 may modulate macrophage activation and mitochondrial metabolism by targeting PI3K/Akt/GSK-3ß signalling pathway, thereby alleviating cytokine storm and inflammation.

Rare case of a patient with testicular torsion complicated by acute pneumonia, requiring emergency surgery, during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has been causing delay in patient arrival at hospital and starting surgery. We report a delay in a case of testicular torsion complicated by acute pneumonia during the COVID-19 pandemic in Japan. CASE PRESENTATION: A 17-year-old Japanese boy presented to our emergency room with acute left scrotum pain and fever in January 2021. It took 2.5 h to transfer him. Physical examination and color Doppler ultrasonography revealed left testicular torsion. Chest computed tomography indicated acute pneumonia. He successfully underwent surgical detorsion 7.5 h after symptom onset, with COVID-19 preventive measures in place. A negative polymerase chain reaction test result for COVID-19 was revealed after surgery. CONCLUSION: We experienced a rare case of testicular torsion complicated by acute pneumonia during the COVID-19 pandemic. Special attention should be paid to preventing infection and surgery delay to avoid testicular loss.

Rugosic acid A, derived from Rosa rugosa Thunb., is novel inhibitory agent for NF-κB and IL-6/STAT3 axis in acute lung injury model.

Rosa rugosa Thunb., is as a medicinal plant known for anti-diabetic, and anti-inflammatory activities. However, the specific active compounds responsible for the individual pharmacological effects of in R. rugosa extract (95% EtOH) remain unknown. Here, we hypothesized that terpenoid structure, the most abundant constituents in R. rugosa extract, are responsible for its anti-inflammatory activity. We investigated the phytochemical substituents (compounds 1-13) and newly purified 11-methoxy polisin A, and 13-methoxy bisaborosaol F using NMR and ESI-MS and to screened their effects on NO production in LPS-induced macrophages. Rugosic acid A (RA) induced to ameliorate NO production, iNOS, and pro-inflammatory cytokines associated with the NF-κB. And, RA suppressed IL-6 secretion and IL-6-mediated STAT3 activation in LPS-mediated inflammation. In addition, RA was evaluated in LPS-mediated acute lung injury (ALI) model similar to acute pneumonia. Our results suggested that RA was suppressed to translocate nuclear NF-κB and IL-6-mediated STAT3 activation. Finally, RA led to amelioration of ALI by decreasing myeloperoxidase (MPO) and inhibiting phosphorylation of NF-κB and STAT3. Our group originally found that R. rugosa extract had new methoxy compounds and RA may be alternative natural agent for acute pneumonia similar to severe acute respiratory syndrome by coronavirus.

A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared with Best Supportive Care in Patients with COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Primary Objective • To evaluate the effect of ravulizumab, a long-acting complement (C5) inhibitor plus best supportive care (BSC) compared with BSC alone on the survival of patients with COVID-19. Secondary Objectives • Number of days free of mechanical ventilation at Day 29 • Duration of intensive care unit stay at Day 29 • Change from baseline in Sequential Organ Failure Assessment (SOFA) score at Day 29 • Change from baseline in peripheral capillary oxygen saturation/ fraction of inspired oxygen (SpO2 /FiO2) at Day 29 • Duration of hospitalization at Day 29 • Survival (based on all-cause mortality) at Day 60 and Day 90 Safety • Incidence of treatment-emergent adverse events and treatment-emergent serious adverse events. PK/PD/Immunogenicity • Change in serum ravulizumab concentrations over time • Change in serum free and total C5 concentrations over time • Incidence and titer of anti-ALXN1210 antibodies Biomarkers • Change in absolute level of soluble biomarkers in blood associated with complement activation, inflammatory processes, and hypercoagulable states over time Exploratory • Incidence of progression to renal failure requiring dialysis at Day 29 • Time to clinical improvement (based on a modified 6-point ordinal scale) over 29 days • SF-12 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores at Day 29 (or discharge), Day 60, and Day 90 • EuroQol 5-dimension 5-level (EQ-5D-5L) scores at Day 29 (or discharge), Day 60, and Day 90 TRIAL DESIGN: This is a multicenter Phase 3, open-label, randomized, controlled, study. The study is being conducted in acute care hospital settings in the United States, United Kingdom, Spain, France, Germany, and Japan. PARTICIPANTS: Male or female patients at least 18 years of age, weighing ≥ 40 kg, admitted to a designated hospital facility for treatment will be screened for eligibility in this study. Key Inclusion criteria • Confirmed diagnosis of SARS-CoV-2 infection (eg, via polymerase chain reaction [PCR] and/or antibody test) presenting as severe COVID-19 requiring hospitalization • Severe pneumonia, acute lung injury, or ARDS confirmed by computed tomography (CT) or X-ray at Screening or within the 3 days prior to Screening, as part of the patient's routine clinical care • Respiratory distress requiring mechanical ventilation, which can be either invasive (requiring endotracheal intubation) or non-invasive (with continuous positive airway pressure [CPAP] or bilevel positive airway pressure [BiPAP]) Key Exclusion criteria • Patient is not expected to survive for more than 24 hours • Patient is on invasive mechanical ventilation with intubation for more than 48 hours prior to Screening • Severe pre-existing cardiac disease (ie, NYHA Class 3 or Class 4, acute coronary syndrome, or persistent ventricular tachyarrhythmias) • Patient has an unresolved Neisseria meningitidis infection Excluded medications and therapies • Current treatment with a complement inhibitor • Intravenous immunoglobulin (IVIg) within 4 weeks prior to randomization on Day 1 Excluded prior/concurrent clinical study experience • Treatment with investigational therapy in a clinical study within 30 days before randomization, or within 5 half-lives of that investigational therapy, whichever is greater • Exceptions a. Investigational therapies will be allowed if received as part of best supportive care through an expanded access protocol or emergency approval for the treatment of COVID-19. b. Investigational antiviral therapies (such as remdesivir) will be allowed even if received as part of a clinical study. INTERVENTION AND COMPARATOR: The study consists of a Screening Period of up to 3 days, a Primary Evaluation Period of 4 weeks, a final assessment at Day 29, and a Follow-up Period of 8 weeks. For patients randomized to ravulizumab plus BSC, a weight-based dose of ravulizumab (≥40 to < 60 kg/2400 mg, 60 to < 100 kg/2700 mg, ≥ 100 kg/3000 mg) will be administered on Day 1. On Day 5 and Day 10, additional doses of 600 mg (≥40 to <60 kg) or 900 mg (>60 kg) ravulizumab will be administered and on Day 15 patients will receive 900 mg ravulizumab. There is no active or placebo comparator in this open-label clinical trial. The total duration of each patient's participation is anticipated to be approximately 3 months. MAIN OUTCOMES: The primary efficacy outcome of this study is survival (based on all-cause mortality) at Day 29. RANDOMISATION: Patients will be randomized in a 2:1 ratio (ravulizumab plus BSC:BSC alone). Randomization will be stratified by intubated or not intubated on Day 1. Computer-generated randomization lists will be prepared by a third party under the direction of the sponsor. Investigators, or designees, will enrol patients and then obtain randomization codes using an interactive voice/web response system. The block size will be kept concealed so that investigators cannot select patients for a particular treatment assignment. Blinding (masking): This is an open-label study. Numbers to be randomised (sample size): Approximately 270 patients will be randomly assigned in a 2:1 ratio to ravulizumab plus BSC (n=180) or BSC alone (n=90). TRIAL STATUS: Protocol Number: ALXN1210-COV-305 Original Protocol: 09 Apr 2020 Protocol Amendment 1 (Global): 13 Apr 2020 Protocol Amendment 2 (Global): 17 Apr 2020 Protocol Amendment 3 (Global): 09 Jun 2020 Recruitment is currently ongoing. Recruitment was initiated on 11 May 2020. We expect recruitment to be completed by 30 Nov 2020. TRIAL REGISTRATION: Clinicaltrials.gov: Protocol Registry Number: NCT04369469 ; First posted; 30 Apr 2020 EU Clinical Trials Register: EudraCT Number: https://www.clinicaltrialsregister.eu/ctr-search/search?query=ALXN1210-COV-305 , Start date: 07 May 2020 FULL PROTOCOL: The full redacted protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

COVID-19 - what should anaethesiologists and intensivists know about it?

Over the past three months, the world has faced an unprecedented health hazard. The World Health Organization has announced a pandemic infection with an unknown species of coronavirus called SARS-CoV-2. Spreading mainly through the droplet route, the virus causes mild symptoms in the majority of cases, the most common being: fever (80%), dry cough (56%), fatigue (22%) and muscle pain (7%); less common symptoms include a sore throat, a runny nose, diarrhea, hemoptysis and chills. A life-threatening complication of SARS-CoV-2 infection is an acute respiratory distress syndrome (ARDS), which occurs more often in older adults, those with immune disorders and co-morbidities. Severe forms of the infection, being an indication for treatment in the intensive care unit, comprise acute lung inflammation, ARDS, sepsis and septic shock. The article presents basic information about etiology, pathogenesis and diagnostics (with particular emphasis on the importance of tomocomputer imaging), clinical picture, treatment and prevention of the infection. It goes on to emphasize the specific risks of providing anesthesiology and intensive care services. Due to the fact that effective causal treatment is not yet available and the number of infections and deaths increases day by day, infection prevention and strict adherence to recommendations of infection control organizations remain the basis for fighting the virus.

Calming Cytokine Storm in Pneumonia by Targeted Delivery of TPCA-1 Using Platelet-Derived Extracellular Vesicles.

Pneumonia can cause high morbidity and mortality because of uncontrolled inflammation in the lung tissue. Calming the cytokine storm may be one key to saving the life of patients with severe pneumonia. Here, inspired by the intrinsic affinity of platelets to the site of inflammation, we have engineered platelet-derived extracellular vesicles (PEVs) for pneumonia-targeted drug delivery. It is demonstrated that PEVs that are easily generated from the activated platelets can selectively target pneumonia in the mouse model with acute lung injury (ALI). By loading with [5-(p-fluorophenyl)-2-ureido]thiophene-3-carboxamide (TPCA-1), which can inhibit the production of inflammatory factors, the PEVs significantly improve therapeutic benefits by inhibiting the infiltration of pulmonary inflammatory cells and calming local cytokine storm compared with the free drug-treated group. Furthermore, we find that PEVs could serve as a broad platform that can selectively target various inflammatory sites, including chronic atherosclerotic plaque, rheumatoid arthritis, and wounds associated with skin.