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Journal of Innate Immunity May 2024Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in... (Review)
Review
Sepsis-associated coagulopathy specifically refers to widespread systemic coagulation activation accompanied by a high risk of hemorrhage and organ damage, which in severe cases manifests as disseminated intravascular coagulation (DIC), or even develops into multiple organ dysfunction syndrome (MODS). The complement system and the coagulation system as the main columns of innate immunity and hemostasis respectively undergo substantial activation after sepsis. Dysfunction of the complement, coagulation/fibrinolytic cascades caused by sepsis leads to "thromboinflammation", which ultimately amplifies the systemic inflammatory response and accelerates the development of MODS. Recent studies have revealed that massive activation of the complement system exacerbates sepsis-induced coagulation and even results in DIC, which suggests that inhibition of complement activation may have therapeutic potential in the treatment of septic coagulopathy. Sepsis-associated thrombosis involves the upregulation or activation of procoagulant factors, down-regulation or inactivation of anticoagulant factors, and impairment of the fibrinolytic mechanism. This review aims to summarize the latest literature and analyze the underlying molecular mechanisms of the activation of the complement system on the abnormal coagulation cascades in sepsis.
PubMed: 38815564
DOI: 10.1159/000539502 -
Kidney360 May 2024
Topics: Humans; Acute Kidney Injury; Sepsis; Oliguria; Male; Kidney; Recovery of Function; Middle Aged
PubMed: 38814758
DOI: 10.34067/KID.0000000000000444 -
Kidney360 May 2024
Topics: Animals; Sepsis; Disease Models, Animal; Humans
PubMed: 38814754
DOI: 10.34067/KID.0000000000000458 -
Clinical Case Reports Jun 2024Methicillin-resistant staph aureus (MRSA) infections are challenging to treat, and with the emergence of community-associated MRSA (CA-MRSA) strains, early consideration...
Methicillin-resistant staph aureus (MRSA) infections are challenging to treat, and with the emergence of community-associated MRSA (CA-MRSA) strains, early consideration of this pathogen in populations without typical risk factors is critical. Here we present a case of CA-MRSA pneumonia that resulted in Community-acquired pneumonia (CAP) with septic shock, pyelonephritis, and muscle abscess.
PubMed: 38813451
DOI: 10.1002/ccr3.8957 -
Frontiers in Medicine 2024Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has had a dramatic...
INTRODUCTION
Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has had a dramatic effect on the world, resulting in millions of deaths worldwide and causing drastic changes in daily life. A study reported that septic complications were associated with high mortality in COVID-19 patients. This study aimed to evaluate how the COVID-19 pandemic changed the pre-pandemic and post-pandemic prevalence of sepsis in ICUs and to evaluate the different risk factors associated with mortality and the different diffusion of microorganisms and their resistance.
MATERIALS AND METHODS
We conducted a single-center retrospective observational clinical study, observing all patients in the ICU of the SS Annunziata Hospital in Chieti (Italy) who were diagnosed with sepsis and had a bacterial isolate from their blood culture. Sepsis was diagnosed by SEPSIIS III criteria. We enrolled all in-patients in the ICU from January 2018 to December 2021. We divided the patients into three groups: (1) non-pandemic period (Np) hospitalized in 2018-2019, (2) pandemic period (Pp)-COVID hospitalized in 2020-2021 with a diagnosis of COVID-19, and (3) Pp-non-COVID patients hospitalized in 2020-2021 without a diagnosis of COVID-19.
RESULTS
From January 2018 to December 2021, 1,559 patients were admitted to the ICU, of which 211 patients [36 (17.1%) in 2018, 52 (24.6%) in 2019, 73 (34.6%) in 2020, and 50 (23.7%) in 2021, respectively] met the selection criteria: 88 patients in period Np, 67 patients in Pp without COVID-19, and 56 patients Pp with COVID-19. The overall mortality of these patients was high (65.9% at 30 days in Np), but decreased during the Pp (60.9%): Pp-non-COVID was 56.7% vs. Pp-COVID 66.1%, with a statistically significant association with APACHE III score (OR 1.08, 95%CI 1.04-1.12, < 0.001), SOFA score (OR 1.12, 95%CI 1.03-1.22, = 0.004), and age (OR 1.04, 95%CI 1.02-1.07, < 0.0001). Between the Np vs. Pp periods, we observed an increase in a few Gram-positive bacteria such as (1 pt. -0.9% vs. 14 pt. -7.65%- = 0.008), , spp., and , as well as a decrease in a case of blood culture positive for , , In Gram-negative bacteria, we observed an increase in cases of spp. (Np 6 pt. -5.1%- vs. Pp 20 pt. -10.9%, = 0.082), and spp., while cases of sepsis decreased from (Np 11 pt. -9.4%- vs. Pp 7 pt. -3.8%, = 0.047), and spp., , spp., and have not changed. Finally, we found that resistance to OXA-48 ( = 0.040), ESBL ( = 0.002), carbapenems ( = 0.050), and colistin ( = 0.003) decreased with time from Np to Pp, particularly in Pp-COVID.
CONCLUSION
This study demonstrated how the COVID-19 pandemic changed the prevalence of sepsis in the ICU. It emerged that the risk factors associated with mortality were APACHE and SOFA scores, age, and, above all, the presence of ESBL-producing bacteria. Despite this, during the pandemic phase, we have observed a significant reduction in the emergence of resistant germs compared to the pre-pandemic phase.
PubMed: 38813381
DOI: 10.3389/fmed.2024.1355144 -
Future Science OA 2024Recently, the emergency of multidrug-resistant organisms (MDRO) has complicated the management of bacterial infections (BI) in cirrhosis. We aimed to assess their...
Recently, the emergency of multidrug-resistant organisms (MDRO) has complicated the management of bacterial infections (BI) in cirrhosis. We aimed to assess their clinical impact on patients with decompensated cirrhosis. A retrospective study included consecutive cirrhotic patients hospitalized for acute decompensation (AD) between January 2010 and December 2019. A total of 518 AD admissions in 219 patients were included, with 260 BI episodes (50.2%). MDRO prevalence was 38.2% of the total isolates. Recent antibiotic use (OR = 4.91), nosocomial infection (OR = 2.95), and healthcare-associated infection (OR = 3.45) were their main risk factors. MDROs were associated with empiric treatment failure (OR = 23.42), a higher prevalence of sepsis (OR = 4.93), ACLF (OR = 3.42) and mortality. The clinical impact of MDROs was pejorative, with an increased risk of empiric treatment failure, organ failure and death.
PubMed: 38813115
DOI: 10.2144/fsoa-2023-0160 -
Saudi Pharmaceutical Journal : SPJ :... Jun 2024Septic shock is associated with systemic inflammatory response, hemodynamic instability, impaired sympathetic control, and the development of multiorgan dysfunction that...
The concomitant use of ultra short beta-blockers with vasopressors and inotropes in critically ill patients with septic shock: A systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Septic shock is associated with systemic inflammatory response, hemodynamic instability, impaired sympathetic control, and the development of multiorgan dysfunction that requires vasopressor or inotropic support. The regulation of immune function in sepsis is complex and varies over time. However, activating Beta-2 receptors and blocking Beta-1 receptors reduces the proinflammatory response by influencing cytokine production. Evidence that supports the concomitant use of ultra short beta-blockers with inotropes and vasopressors in patients with septic shock is still limited. This study aimed to evaluate the use of ultra short beta-blockers and its impact on the ICU related outcomes such as mortality, length of stay, heart rate control, shock resolution, and vasopressors/inotropes requirements.
METHODS
A systematic review and meta-analysis of randomized controlled trials including critically ill patients with septic shock who received inotropes and vasopressors. Patients who received either epinephrine or norepinephrine without beta-blockers "control group" were compared to patients who received ultra short beta-blockers concomitantly with either epinephrine or norepinephrine "Intervention group". MEDLINE and Embase databases were utilized to systematically search for studies investigating the use of ultra short beta-blockers in critically ill patients on either epinephrine or norepinephrine from inception to October 10, 2023. The primary outcome was the 28-day mortality. While, length of stay, heart rate control, and inotropes/ vasopressors requirements were considered secondary outcomes.
RESULTS
Among 47 potentially relevant studies, nine were included in the analysis. The 28-day mortality risk was lower in patients with septic shock who used ultra short beta-blockers concomitantly with either epinephrine or norepinephrine compared with the control group (RR (95%CI): 0.69 (0.53, 0.89), 2=26%;=0.24). In addition, heart rate was statistically significantly lower with a standardized mean difference (SMD) of -22.39 (95% CI: -24.71, -20.06) among the beta-blockers group than the control group. The SMD for hospital length of stay and the inotropes requirement were not statistically different between the two groups (SMD (95%CI): -0.57 (-2.77, 1.64), and SMD (95%CI): 0.08 (-0.02, 0.19), respectively).
CONCLUSION
The use of ultra short beta-blockers concomitantly with either epinephrine or norepinephrine in critically ill patients with septic shock was associated with better heart rate control and survival benefits without increment in the inotropes and vasopressors requirement.
PubMed: 38812943
DOI: 10.1016/j.jsps.2024.102094 -
Turkish Journal of Medical Sciences 2024Extracorporeal blood purification (EBP) therapies have shown promise as potential rescue treatments for patients with septic shock. However, precise evidence regarding...
BACKGROUND/AIM
Extracorporeal blood purification (EBP) therapies have shown promise as potential rescue treatments for patients with septic shock. However, precise evidence regarding their effectiveness is lacking. This case-control study aimed to evaluate the 28-day survival benefit of a resin cartridge-based EBP therapy compared to conventional therapies in patients with septic shock.
MATERIALS AND METHODS
The study sample was collected retrospectively from the medical records of patients admitted to the intensive care unit (ICU) between 2015 and 2020. The study included patients with septic shock aged ≥18 years who had ICU stays >96 h and excluded those lost to follow-up by 28 days or readmitted. First, 28-day survival was compared between EBP patients and 1:1 matched conventionally treated controls. Second, the EBP patients were evaluated for clinical and laboratory improvements within 72 h of EBP therapy.
RESULTS
Of 3742 patients, 391 were included in this study, of whom 129 received EBP therapy and had a 28-day survival rate of 44%, compared to 262 matched controls who received conventional therapy alone and had a survival rate of 33% (p = 0.001, log-rank = 0.05, number needed to treat = 8, and odds ratio = 1.7). After receiving EBP therapy for 72 h, improvements were observed in the Sequential Organ Failure Assessment scores (p < 0.05), shock indices (p < 0.05), partial pressure of oxygen in the arterial blood to the fraction of inspiratory oxygen concentration ratios (p < 0.001), vasopressor requirements (p < 0.001), pH (p < 0.05), lactate levels (p < 0.001), and C-reactive protein levels (p < 0.05).
CONCLUSION
The findings suggest that administering resin cartridge-based EBP therapy to patients with septic shock may improve their survival compared to conventional therapies.
Topics: Humans; Shock, Septic; Male; Female; Middle Aged; Retrospective Studies; Case-Control Studies; Aged; Hemofiltration; Survival Rate; Treatment Outcome; Intensive Care Units; Adult
PubMed: 38812634
DOI: 10.55730/1300-0144.5773 -
Critical Care (London, England) May 2024Critical illness syndromes including sepsis, acute respiratory distress syndrome, and acute kidney injury (AKI) are associated with high in-hospital mortality and... (Review)
Review
Critical illness syndromes including sepsis, acute respiratory distress syndrome, and acute kidney injury (AKI) are associated with high in-hospital mortality and long-term adverse health outcomes among survivors. Despite advancements in care, clinical and biological heterogeneity among patients continues to hamper identification of efficacious therapies. Precision medicine offers hope by identifying patient subclasses based on clinical, laboratory, biomarker and 'omic' data and potentially facilitating better alignment of interventions. Within the previous two decades, numerous studies have made strides in identifying gene-expression based endotypes and clinico-biomarker based phenotypes among critically ill patients associated with differential outcomes and responses to treatment. In this state-of-the-art review, we summarize the biological similarities and differences across the various subclassification schemes among critically ill patients. In addition, we highlight current translational gaps, the need for advanced scientific tools, human-relevant disease models, to gain a comprehensive understanding of the molecular mechanisms underlying critical illness subclasses.
Topics: Humans; Critical Illness; Sepsis; Acute Kidney Injury; Respiratory Distress Syndrome; Biomarkers; Precision Medicine
PubMed: 38812006
DOI: 10.1186/s13054-024-04959-3 -
Journal of Biomedical Science May 2024Severe infection and sepsis are medical emergencies. High morbidity and mortality are linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy... (Review)
Review
Severe infection and sepsis are medical emergencies. High morbidity and mortality are linked to CNS dysfunction, excessive inflammation, immune compromise, coagulopathy and multiple organ dysfunction. Males appear to have a higher risk of mortality than females. Currently, there are few or no effective drug therapies to protect the brain, maintain the blood brain barrier, resolve excessive inflammation and reduce secondary injury in other vital organs. We propose a major reason for lack of progress is a consequence of the treat-as-you-go, single-nodal target approach, rather than a more integrated, systems-based approach. A new revolution is required to better understand how the body responds to an infection, identify new markers to detect its progression and discover new system-acting drugs to treat it. In this review, we present a brief history of sepsis followed by its pathophysiology from a systems' perspective and future opportunities. We argue that targeting the body's early immune-driven CNS-response may improve patient outcomes. If the barrage of PAMPs and DAMPs can be reduced early, we propose the multiple CNS-organ circuits (or axes) will be preserved and secondary injury will be reduced. We have been developing a systems-based, small-volume, fluid therapy comprising adenosine, lidocaine and magnesium (ALM) to treat sepsis and endotoxemia. Our early studies indicate that ALM therapy shifts the CNS from sympathetic to parasympathetic dominance, maintains cardiovascular-endothelial glycocalyx coupling, reduces inflammation, corrects coagulopathy, and maintains tissue O supply. Future research will investigate the potential translation to humans.
Topics: Humans; Sepsis; Adenosine; Lidocaine; Magnesium; Fluid Therapy
PubMed: 38811967
DOI: 10.1186/s12929-024-01043-4