Targeting the host response in sepsis: current approaches and future evidence

Critical Care, Год журнала: 2023, Номер 27(1)

Опубликована: Дек. 6, 2023

Abstract Sepsis, a dysregulated host response to infection characterized by organ failure, is one of the leading causes death worldwide. Disbalances immune play an important role in its pathophysiology. Patients may develop simultaneously or concomitantly states systemic local hyperinflammation and immunosuppression. Although variety effective immunomodulatory treatments are generally available, attempts inhibit stimulate system sepsis have failed so far improve patients’ outcome. The underlying reason likely multifaceted including failure identify responders specific intervention complex pathophysiology dysfunction that not exclusively caused immunopathology but also includes coagulation system, parenchymal organs, endothelium. Increasing evidence suggests stratification heterogeneous population septic patients with consideration their might led more effective. purpose this review provide overview current studies aimed at optimizing many facets discuss future perspectives for precision medicine approaches sepsis.

Язык: Английский

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Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Ноя. 7, 2024

Hemophagocytic lymphohistiocytosis (HLH) is a rapidly progressing, life-threatening syndrome characterized by excessive immune activation, often presenting as complex cytokine storm. This hyperactive response can lead to multi-organ failure and systemic damage, resulting in an extremely short survival period if left untreated. Over the past decades, although HLH has garnered increasing attention from researchers, there have been few advancements its treatment. The storm plays crucial role treatment of HLH. Investigating detailed mechanisms behind storms offers insights into targeted therapeutic approaches, potentially aiding early intervention improving clinical outcome patients. To date, only one therapy, emapalumab targeting interferon-γ, that gained approval for primary review aims summarize current advances, emerging therapeutics underlying HLH, highlighting newly discovered targets involved storms, which are expected drive development novel treatments offer fresh perspectives future studies. Besides, multi-targeted combination therapy may be essential disease control, but further trials required determine optimal mode

Язык: Английский

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mTORC1 syndrome (TorS): unifying paradigm for PASC, ME/CFS and PAIS

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Март 9, 2025

Post-acute SarS-Cov2 (PASC), Myalgia encephalomyelitis/Chronic fatigue syndrome (ME/CFS) and infection (PAIS) consist of chronic post–acute infectious syndromes, sharing exhaustive fatigue, post exertional malaise, intermittent pain, postural tachycardia neuro-cognitive-psychiatric dysfunction. However, the concerned shared pathophysiology is still unresolved in terms upstream drivers transducers. Also, risk factors which may determine vulnerability/progression to phase remain be defined. In lack a cohesive pathophysiology, syndromes unmet therapeutic needs. 'mTORC1 Syndrome' (TorS) implies an disease entity driven by sustained hyper-activation mammalian target rapamycin C1 (mTORC1), resulting variety aspects Metabolic Syndrome (MetS), non-alcoholic fatty liver disease, obstructive pulmonary some cancers, neurodegeneration other [Bar-Tana Trends Endocrinol Metab 34:135–145, 2023]. TorS offer insight PASC, ME/CFS PAIS drivers, vulnerability treatment options.

Язык: Английский

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Estimates of actual and potential lives saved in the United States from the use of COVID-19 convalescent plasma

Proceedings of the National Academy of Sciences, Год журнала: 2024, Номер 121(41)

Опубликована: Окт. 1, 2024

In the Spring of 2020, United States America (USA) deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Over 500,000 patients were treated with CCP during first year pandemic. this study, we estimated number actual inpatient lives saved by treatment in based on weekly use, national mortality data, and reduction data from meta-analyses randomized controlled trials real-world data. We also estimate potential if had been for 100% or used 15 75% outpatients. Depending assumptions modeled stratified analyses, that between 16,476 66,296 lives. The ideal use might have as many 234,869 prevented 1,136,133 hospitalizations. deployment was a successful strategy ameliorating impact pandemic USA. This experience has important implications future infectious disease emergencies.

Язык: Английский

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Efficacy and safety of tocilizumab versus standard care/placebo in patients with COVID‐19; a systematic review and meta‐analysis of randomized clinical trials

British Journal of Clinical Pharmacology, Год журнала: 2021, Номер 88(5), С. 1955 - 1963

Опубликована: Окт. 29, 2021

Tocilizumab has emerged as an important therapy in treating patients with coronavirus disease (COVID-19). Our purpose was to evaluate the efficacy and safety of tocilizumab versus standard care/placebo COVID-19.

Язык: Английский

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Influence of extracorporeal cytokine adsorption on hemodynamics in severe acute pancreatitis: Results of the matched cohort pancreatitis cytosorbents inflammatory cytokine removal (PACIFIC) study

Artificial Organs, Год журнала: 2022, Номер 46(6), С. 1019 - 1026

Опубликована: Фев. 19, 2022

Outcome of severe acute pancreatitis (SAP) highly depends on the degree systemic inflammation and organ failure. Although treatment approaches targeting inflammatory cascade have failed in pancreatitis, recent studies suggest that extracorporeal cytokine adsorption effectively reduces concentrations pro-inflammatory cytokines potentially improves outcome sepsis.Sixteen patients with SAP, presenting within 7 days upon onset pain, an APACHE-II score ≥10 ≥1 marker poor prognosis, received 2 consecutive 24-h treatments CytoSorb® (intervention group). Hemodynamics, failure, mortality were compared score-matched retrospective control group 32 patients.The primary objective (20% decrease vasopressor dependency index or 20% increase cardiac index) was reached 68.8% intervention 28.1% (p = 0.007), respectively. The significantly reduced IL-6 (-1998 pg/ml, p 0.005) serum levels resulted stable CRP 0.101) decreased PCT 0.003) contrast to increased 0.014) 0.695) group. While improvement respiratory failure similar both groups, renal improved (change KDIGO classification 72 h postcytokine [-1 vs. 0, 0.005]) SOFA (day 5: -1.8 ± 2.0 1 3.8, 0.013) group.Cytokine might be effective option stabilize hemodynamics SAP. It decreases stabilizes function according serial assessments.

Язык: Английский

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Current treatment challenges in the COVID-19 pandemic

Polskie Archiwum Medycyny Wewnętrznej, Год журнала: 2021, Номер 131(9), С. 854 - 861

Опубликована: Сен. 30, 2021

Infection with SARS-CoV-2, responsible for COVID-19, has spread all over the world since beginning of 2020. Healthcare providers and researchers have been overwhelmed not only by rapid diffusion disease resulting in a pandemic more than 4 million cases death, but also lack therapeutic options. After 1 year, knowledge on COVID-19 increased thanks to enormous effort scientific community. To date, some algorithms management adopted. While asymptomatic or mildly symptomatic patients should receive symptom-based treatment clinical monitoring when necessary, inpatients could be candidates antiviral due fully disease. Corticosteroid limited severe disease, particularly those respiratory failure acute distress syndrome. Since main features are hypoxemia dyspnea, oxygen therapy remains cornerstone managing cases. In this context, first-line approach represented low-flow delivery via nasal cannula or, frequently, face mask known fraction inspired oxygen. When fails significantly improve saturation, using high-flow is recommended. The current challenges include need define role convalescent plasma monoclonal antibodies as well identify optimal target time anticoagulation. review, we highlight aspects these light recent updates.

Язык: Английский

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Mesenchymal Stem Cells in the Treatment of COVID-19

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(19), С. 14800 - 14800

Опубликована: Сен. 30, 2023

Since the emergence of coronavirus disease 2019 (COVID-19) pandemic, many lives have been tragically lost to severe infections. The COVID-19 impact extends beyond respiratory system, affecting various organs and functions. In cases, it can progress acute distress syndrome (ARDS) multi-organ failure, often fueled by an excessive immune response known as a cytokine storm. Mesenchymal stem cells (MSCs) considerable potential because they mitigate inflammation, modulate responses, promote tissue regeneration. Accumulating evidence underscores efficacy safety MSCs in treating ARDS. Nonetheless, critical aspects, such optimal routes MSC administration, appropriate dosage, treatment intervals, management extrapulmonary complications, pediatric applications, warrant further exploration. These research avenues hold promise for enriching our understanding refining application confronting multifaceted challenges posed COVID-19.

Язык: Английский

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Kinetics of pro- and anti-inflammatory spike-specific cellular immune responses in long-term care facility residents after COVID-19 mRNA primary and booster vaccination: a prospective longitudinal study in Japan

Immunity & Ageing, Год журнала: 2024, Номер 21(1)

Опубликована: Июнь 22, 2024

Abstract Background The magnitude and durability of cell-mediated immunity in older severely frail individuals following coronavirus disease 2019 (COVID-19) vaccination remain unclear. A controlled immune response could be the key to preventing severe COVID-19; however, it is uncertain whether induces an anti-inflammatory cellular response. To address these issues, a 48-week-long prospective longitudinal study was conducted. total 106 infection-naive participants (57 long-term care facility [LTCF] residents [median age; 89.0 years], 28 outpatients 72.0 21 healthcare workers 51.0 years]) provided peripheral blood mononuclear cell (PBMC) samples for assessment spike-specific PBMC responses before primary vaccination, 24 weeks after three months booster vaccination. Cellular acute respiratory syndrome 2 spike protein were examined by measuring interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-2, IL-4, IL-6, IL-10 levels secreted from peptide-stimulated PBMCs participants. Results LTCF exhibited significantly lower IFN-γ, TNF, IL-2, IL-6 than Booster increased IL-2 comparable those workers, whereas IFN-γ TNF remained workers. not different initial values but all subgroups. Multivariate analysis showed that age negatively associated with levels. pro-inflammatory cytokines, including positively correlated humoral responses, not. Conclusions Older may exhibit diminished COVID-19 compared general population. single adequately enhance level Furthermore, induce only also response, potentially mitigating detrimental hyperinflammation.

Язык: Английский

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Respiratory disorders

Oxford University Press eBooks, Год журнала: 2025, Номер unknown, С. 365 - 406

Опубликована: Фев. 1, 2025

Abstract This chapter covers diagnosis and management of key disorders the respiratory system seen in intensive care unit. The starts with common presenting problems such as dyspnoea, airway obstruction, failure. It then specific conditions atelectasis pulmonary collapse, pneumonia, COVID-19, acute distress syndrome, chronic obstructive disease, severe asthma. finishes sections on pneumothorax, haemothorax, haemoptysis, inhalation injury, embolus.

Язык: Английский

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