Global research trends on sepsis and septic shock during 2003–2022: A data-driven bibliometric analysis (preprint)

Background Sepsis is a major medical condition that contributes to substantial morbidity and mortality rates worldwide. Research to better understand and manage these complex conditions has intensified over the past two decades. This bibliometric analysis aims to map global research trends in sepsis and septic shock from 2003 to 2022, providing insights into the evolution of the field.Methods This study conducted a comprehensive search for publications on sepsis and septic shock using the Web of Science Core Collection. Data were analysed using VOSviewer for bibliometric mapping, focusing on publication trends, country, institutional contributions, journal sources, citation analysis, and keyword co-occurrence.Results In total, 78,108 publications were retrieved, with a notable increase in annual output over the study period. The United States ranked first in publication volume, followed by China, Germany, and the United Kingdom. Harvard University was the most prolific institution. Critical Care Medicine emerged as the leading journal in terms of publication count. The most cited articles and references were predominantly related to definition, epidemiology, and management guidelines for sepsis. Recent research hotspots included COVID-19, machine learning applications, NLRP3 inflammasome, autophagy, gut microbiota, and microRNA (miRNA).Conclusions Our bibliometric analysis identifies global research trends in sepsis over the past 20 years, with evolving hotspots and increasing global collaboration. Key findings highlight continuous efforts to understand the complex pathophysiology of sepsis and septic shock. COVID-19, machine learning applications, NLRP3 inflammasome, autophagy, gut microbiota, and microRNA (miRNA) are hotspots.

The Role of Serum Albumin and Blood Urea Nitrogen to Serum Albumin Ratio in Prediction of Disease Severity and Thirty--day Mortality in Patients with COVID--19 (preprint)

Background: Considering the role of higher blood urea nitrogen and lower serum albumin (SA) levels in deceased COVID-19 patients, increased blood urea nitrogen to SA (B/A) ratio may help to determine those at higher risk of becoming critically ill. This study evaluated the association of SA level and B/A ratio with disease severity and 30–day mortality and also their predictive value for disease severity in COVID–19 patients. Methods: 433 adult patients with COVID–19, admitted to a referral medical center in Tehran, Iran, from February to May 2020 were included. The laboratory markers were measured on admission. Disease severity was categorized into mild disease, severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis, and septic shock. The mortality was followed up for thirty days after admission. Results: Thirty–day mortality rate was 27.25%. The frequency of mild, severe pneumonia, ARDS, sepsis, and septic shock was 30.72%, 36.95%, 24.02%, 6.00%, and 2.31%, respectively. Mean B/A ratio was different among different disease severities. The odds of thirty-day mortality increased by 16% by each unit increase in B/A ratio and decreased by 57% by each unit increase in SA level. B/A ratio had the AUC of 0.45 for disease severity prediction with 71% sensitivity and 22% specificity. Conclusion: The results showed that B/A ratio and SA levels are associated with mortality in COVID–19 patient, while they had low predictive value for disease severity. High B/A ratio is, additionally, associated with disease severity. Therefore, we suggest to use this marker for clinical assessment of patients with COVID–19.

Convalescent Plasma for Critically-ill Covid-19 Patients (preprint)

Background and aim: Convalescent plasma (CP) was early and successfully used in management of covid-19 infection. This report aimed to document our experience with use of CP in two critically-ill covid-19 patients.Main findings: Patients presented with fever, dry cough and difficulty of breathing with reduced oxygen saturation, massive radiological lung involvement and deteriorated Sequential Organ Failure Assessment (SOFA) Score. Use of two sessions of CP resulted in marked improvement of radiological and/or pulmonary findings. Both patients died of septic shock or thromboembolic events.Conclusions Use of CP may be associated with radiological and clinical improvement in critically-ill patients. However, it’s not related to better survival if used in late stages of the disease.

Addressing the aftermath of the COVID-19 pandemic: A quality improvement collaborative to optimize the use of antibacterials in Argentine Intensive Care Units (preprint)

BackgroundReducing antimicrobial resistance is a global priority that become even more important after the COVID-19 pandemic. To date there is a scarce volume of evidence from antimicrobial stewardship programs from less resourced settings where this phenomenon is bigger. Our aim was to improve the quality of antibacterials prescription in intensive care units (ICUs) in a middle-income country. MethodsWe established a quality improvement collaborative (QIC) model involving nine ICUs over an 11-month period, with a 16-week baseline (BP) and 32-week Intervention (IP) periods. Our co-designed intervention package included audits and feedback on antibacterial use, facility-specific treatment guidelines, antibacterial timeouts, pharmacy-based interventions, and education. The intervention was delivered in two learning sessions with three action periods, along with coaching support and basic quality improvement training. ResultsWe enrolled 912 patients, with 357 in baseline period (BP) and 555 in implementation period (IP). The latter had higher APACHE II (17 (12, 21) vs. 15 (11, 20); p=0.036) and SOFA scores (6 (4, 9) vs. 5 (3, 8); p=0.006), sepsis (36.1% vs. 31.6%, p<0.001), and septic shock (40.0% vs. 33.8%, p<0.001). Days of antibacterial therapy were similar between groups (IP 1112.2, BP 1133.4, RR 0.98 (0.95-1.02); p=0.2973) and the antibacterial Daily Define Dose was lower in IP group (IP, 1193.0; BP, 1301.0; RR, 0.92 (0.89, 0.95); p=0.0001). The rate of adequate antibacterial adjustment was higher during the IP (62.0% vs. 45.3%, p<0.001). We observed a lower rate of ventilation-associated pneumonia and catheter-associated urinary tract infections related to multidrug-resistant organisms (MDRO) in the IP. There was a noticeable improvement in the Infection Prevention and Control (IPC) Assessment Framework compared to baseline. ConclusionThe implementation of a post pandemic antimicrobial stewardship program in ICUs via a QIC demonstrated success in improving antibacterials utilization, reducing HAIs related to MDRO while also enhancing IPC measures. What is already known on this topicO_LIHealthcare-associated infections represent a global healthcare issue, particularly prevalent in low- and middle-income countries, where their occurrence is nearly three times higher. C_LIO_LIApproximately 50% of antimicrobial use is deemed unnecessary or inappropriate, necessitating the development of widely accessible stewardship methods. C_LIO_LIThe misuse and overuse of antibacterials adversely affect patients admitted to intensive care units (ICUs). C_LIO_LIFurther research is urgently required to determine the most effective ways to implement ASPs in LMICs. C_LI What this study addsO_LIBy establishing a quality improvement collaborative (QIC), we showcased an improvement in antibacterial utilization within ICUs in a low- to middle-income country. C_LIO_LIAdditionally, a reduction in healthcare-associated infections is evident. C_LIO_LIMoreover, the QIC effectively strengthened the capabilities of infection control and prevention in participating ICUs. C_LI How this study might affect research, practice, or policyO_LIThis study is among the initial endeavors in a middle-income country to evaluate the efficacy and essential strategies for establishing antimicrobial stewardship programs. C_LIO_LIThis study could serve as a foundational reference for upcoming teams aiming to introduce similar programs in the region. C_LI

Clinical and Genomic Evaluations of a persistent fatal SARS-CoV-2 infection in a Goods syndrome patient: A case report (preprint)

COVID-19 resulted from an infection by SARS-Cov-2 which is the main cause of ADRS in global population from 2019 on. It may contribute to higher rate of death among the patients with immunodeficiency based on recent reports. In addition, Good syndrome (GS) as a result of thymoma removal might cause in some long-lasting microbial infections. We described clinical aspects and viral mutations on a case of GS suffering from COVID-19. A 46-year-old man with fever, general respiratory signs and positive COVID-19 PCR test, with the history of thymoma removal surgery was admitted to Masih Daneshvari Hospital, Tehran, Iran. Lung radiographs and Oxygen saturation measurement disclosed considerable implication resulted in application of several anti-microbial medication. The delta variant (B.1.617.2 (21J Clade)) was the strain isolated from the patient by sequencing methods done by CNRL while the dominant strain circulated mostly among population was Omicron (B.1.1.529) at the time of sampling. Unfortunately, the patient had passed away a month later by sudden respiratory failure progressed in refractory septic shock. Despite the fact that opportunistic infections may lead the GS patients to a major health problematic condition, unusual persistent of infections such as non-dominant variant of SARS-Cov-2 could be observed through the disease timeline. Therefore, a fully screening of thymoma plus intra-host evolution monitoring of SARS-CoV-2 is highly recommended in immunocompromised patients.

Sepsis in the Pediatric Cardiac Intensive Care Unit: An Updated Review.

Sepsis remains among the most common causes of mortality in children with congenital heart disease (CHD). Extensive literature is available regarding managing sepsis in pediatric patients without CHD. Because the cardiovascular pathophysiology of children with CHD differs entirely from their typical peers, the available diagnosis and management recommendations for sepsis cannot be implemented directly in children with CHD. This review discusses the risk factors, etiopathogenesis, available diagnostic tools, resuscitation protocols, and anesthetic management of pediatric patients suffering from various congenital cardiac lesions. Further research should focus on establishing a standard guideline for managing children with CHD with sepsis and septic shock admitted to the intensive care unit.

Randomized Clinical Trial of Antioxidant Therapy Patients with Septic Shock and Organ Dysfunction in the ICU: SOFA Score Reduction by Improvement of the Enzymatic and Non-Enzymatic Antioxidant System.

BACKGROUND AND AIM: Here, we assess the effect of adjuvant antioxidant therapies in septic shock patients with organ dysfunction and their effect on the enzymatic and non-enzymatic antioxidant systems. METHODS: Randomized clinical trial run between 2018 and 2022. One hundred and thirty-one patients with septic shock were included in five groups with 25, 27, 24, 26 and 29 patients each. Group 1 received vitamin C (Vit C), Group 2 vitamin E (Vit E), Group 3 n-acetylcysteine (NAC), Group 4 melatonin (MT) and group 5 no treatment. All antioxidants were administered orally or through a nasogastric tube for 5 days as an adjuvant to standard therapy. RESULTS: All patients had multiple organ failure (MOF) and low Vit C levels. Vit C therapy decreased CRP, PCT and NO3-/NO2- but increased Vit C levels. The SOFA score decreased with MT in 75%, Vit C 63% and NAC 50% vs. controls 33% (p = 0.0001, p = 0.03 and p = 0.001 respectively). MT diminished lipid peroxidation (LPO) (p = 0.01) and improved total antioxidant capacity (TAC) (p = 0.04). Vit E increased thiol levels (p = 0.02) and tended to decrease LPO (p = 0.06). Selenium levels were decreased in the control group (p = 0.04). CONCLUSIONS: Antioxidants used as an adjuvant therapy in the standard treatment of septic shock decrease MOF and oxidative stress markers. They increase the TAC and thiols, and maintain selenium levels.

The Importance of Shifting Sepsis Quality Measures From Processes to Outcomes.

This Viewpoint discusses the failure of the Centers for Medicare & Medicaid Services' SEP-1 sepsis outcome improvement initiative to improve patients' sepsis outcomes and suggests changing the focus of sepsis quality metrics from processes to outcomes.

Hemoperfusion techniques using Jafron HA330 cartridge combined with BBraun Dialog+ dialysis machine in patient with coronavirus disease 2019 pneumonia and septic shock: a case report.

BACKGROUND: The use of hemoperfusion for cytokine removal and inflammatory mediators is increasingly intense, especially in coronavirus disease 2019 patients who are already known to the general public for having cytokine storms. However, we have known about these cytokine storms for a long time in the critical care world. One of the modalities to remove cytokines is to use filtration and adsorption techniques with continuous renal replacement therapy. The use of continuous renal replacement therapy is usually constrained by its very high cost compared with standard care, especially in Indonesia, where health costs are covered by national health insurance. In this case, we use hemodialysis and hemoperfusion, using a dialysis machine, which is more cost-effective and easy to use. CASE PRESENTATION: We used the Jafron HA330 cartridge, modified for the BBraun Dialog+ dialysis machine. This case report presents an 84-year-old Asian man with septic shock due to pneumonia, congestive heart failure, and acute chronic kidney disease accompanied by fluid overload. After undergoing hemodialysis and hemoperfusion separately, there was a gradual and significant clinical improvement. Clinical indicators, including the vasopressor inotropic score and infection markers, should all be considered when deciding whether to begin hemodialysis and hemoperfusion. CONCLUSION: In general, using hemoperfusion to treat septic shock patients can reduce the length of stay in the intensive care unit, and morbidity and mortality.

Extracorporeal blood purification benefits in post-caesarean patient with severe acute respiratory distress syndrome due to miliary tuberculosis: a case report.

BACKGROUND: Miliary tuberculosis is a life-threatening disease caused by the hematogenous spread of Mycobacterium tuberculosis. It is uncommon in pregnancy. Mortality rates for patients with miliary tuberculosis who require mechanical ventilation are high (60-70%). CASE PRESENTATION: We reported a rare and challenging case, a 35-year-old Asian woman with 34 weeks of pregnancy, and miliary tuberculosis with acute respiratory distress syndrome and septic shock. The patient presented with severe acute respiratory distress syndrome, necessitating mechanical ventilation, vasopressor, and pregnancy termination with caesarean section. The patient underwent blood purification with continuous veno-venous hemofiltration using an oXiris filter for 24 hours. After continuous veno-venous hemofiltration, the patient's condition was greatly improved, and the patient was successfully extubated and was able to breathe spontaneously without vasopressor on the third day. High levels of interleukin-6, interleukin-10, procalcitonin, C-reactive protein, interferon-γ, and tumor necrosis factor-α were found postoperatively. CONCLUSION: The bacterial infection of tuberculosis, acute respiratory distress syndrome, and the stress response from the caesarean section contributed to the high levels of cytokines, which correlated with the patient's severe inflammatory condition. The cytokine levels were greatly reduced after the blood purification procedure and this might be associated with the patient's clinical improvement. Extracorporeal blood purification could help to disrupt the vicious cycle of inflammation.

Evaluation of steroid therapy in COVID-19 patients; in the right dose at the right time to the right patients.

Background: Although there is still no universally accepted treatment agent, steroids have been administered chronologically at every dose and at every stage of the COVID-19 pandemic. Aim: We aimed to evaluate the clinical efficacy of high-dose steroid therapy and its effect on mortality in COVID-19 patients with severe pneumonia, severe Acute Respiratory Distress Syndrome (ARDS), and septic shock. Patients and Methods: : Patients with severe pneumonia, septic shock, and ARDS due to COVID-19 who were followed up in the intensive care unit were retrospectively reviewed. Results: The study population was divided into two groups; the methylprednisolone pulse group (MP) (n = 55) and the dexamethasone group (Dex) (n = 39). When the values before and after treatment were compared; there was a statistically significant increase in the neutrophil/lymphocyte ratio after treatment in the MP group (p = 0.006). Although it was not statistically significant in the MP group, There was a numerical increase in D-dimer levels (p = 0.28). Thromboembolic complications developed in 2 patients in the MP group. The mortality outcomes of the groups were statistically similar (p = 0.943). Conclusion: We recommend steroids use in the condition that it is indicated in the critically ill group with the poor general condition. Since there is no significant difference between high-dose pulse steroid treatment and standard treatment doses, we think that the risk of complications should not be taken into account and high doses should not be used.

Recent nanoengineered diagnostic and therapeutic advancements in management of Sepsis.

COVID-19 acquired symptoms have affected the worldwide population and increased the load of Intensive care unit (ICU) patient admissions. A large number of patients admitted to ICU end with a deadly fate of mortality. A high mortality rate of patients was reported with hospital-acquired septic shock that leads to multiple organ failures and ultimately ends with death. The patients who overcome this septic shock suffer from morbidity that also affects their caretakers. To overcome these situations, scientists are exploring progressive theragnostic techniques with advanced techniques based on biosensors, biomarkers, biozymes, vesicles, and others. These advanced techniques pave the novel way for early detection of sepsis-associated symptoms and timely treatment with appropriate antibiotics and immunomodulators and prevent the undue effect on other parts of the body. There are other techniques like externally modulated electric-based devices working on the principle of piezoelectric mechanism that not only sense the endotoxin levels but also target them with a loaded antibiotic to neutralize the onset of inflammatory response. Recently researchers have developed a lipopolysaccharide (LPS) neutralizing cartridge that not only senses the LPS but also appropriately neutralizes with dual mechanistic insights of antibiotic and anti-inflammatory effects. This review will highlight recent developments in the new nanotechnology-based approaches for the diagnosis and therapeutics of sepsis that is responsible for the high number of deaths of patients suffering from this critical disease.

Early adjunctive methylene blue in patients with septic shock: a randomized controlled trial.

PURPOSE: Methylene blue (MB) has been tested as a rescue therapy for patients with refractory septic shock. However, there is a lack of evidence on MB as an adjuvant therapy, its' optimal timing, dosing and safety profile. We aimed to assess whether early adjunctive MB can reduce time to vasopressor discontinuation in patients with septic shock. METHODS: In this single-center randomized controlled trial, we assigned patients with septic shock according to Sepsis-3 criteria to MB or placebo. Primary outcome was time to vasopressor discontinuation at 28 days. Secondary outcomes included vasopressor-free days at 28 days, days on mechanical ventilator, length of stay in ICU and hospital, and mortality at 28 days. RESULTS: Among 91 randomized patients, forty-five were assigned to MB and 46 to placebo. The MB group had a shorter time to vasopressor discontinuation (69 h [IQR 59-83] vs 94 h [IQR 74-141]; p < 0.001), one more day of vasopressor-free days at day 28 (p = 0.008), a shorter ICU length of stay by 1.5 days (p = 0.039) and shorter hospital length of stay by 2.7 days (p = 0.027) compared to patients in the control group. Days on mechanical ventilator and mortality were similar. There were no serious adverse effects related to MB administration. CONCLUSION: In patients with septic shock, MB initiated within 24 h reduced time to vasopressor discontinuation and increased vasopressor-free days at 28 days. It also reduced length of stay in ICU and hospital without adverse effects. Our study supports further research regarding MB in larger randomized clinical trials. Trial registration ClinicalTrials.gov registration number NCT04446871 , June 25, 2020, retrospectively registered.

The relationship between high density lipoprotein cholesterol and sepsis: A clinical and genetic approach.

Sepsis accounts for one in three hospital deaths. Higher concentrations of high-density lipoprotein cholesterol (HDL-C) are associated with apparent protection from sepsis, suggesting a potential therapeutic role for HDL-C or drugs, such as cholesteryl ester transport protein (CETP) inhibitors that increase HDL-C. However, these beneficial clinical associations might be due to confounding; genetic approaches can address this possibility. We identified 73,406 White adults admitted to Vanderbilt University Medical Center with infection; 11,612 had HDL-C levels, and 12,377 had genotype information from which we constructed polygenic risk scores (PRS) for HDL-C and the effect of CETP on HDL-C. We tested the associations between predictors (measured HDL-C, HDL-C PRS, CETP PRS, and rs1800777) and outcomes: sepsis, septic shock, respiratory failure, and in-hospital death. In unadjusted analyses, lower measured HDL-C concentrations were significantly associated with increased risk of sepsis (p = 2.4 × 10-23 ), septic shock (p = 4.1 × 10-12 ), respiratory failure (p = 2.8 × 10-8 ), and in-hospital death (p = 1.0 × 10-8 ). After adjustment (age, sex, electronic health record length, comorbidity score, LDL-C, triglycerides, and body mass index), these associations were markedly attenuated: sepsis (p = 2.6 × 10-3 ), septic shock (p = 8.1 × 10-3 ), respiratory failure (p = 0.11), and in-hospital death (p = 4.5 × 10-3 ). HDL-C PRS, CETP PRS, and rs1800777 significantly predicted HDL-C (p < 2 × 10-16 ), but none were associated with sepsis outcomes. Concordant findings were observed in 13,254 Black patients hospitalized with infections. Lower measured HDL-C levels were significantly associated with increased risk of sepsis and related outcomes in patients with infection, but a causal relationship is unlikely because no association was found between the HDL-C PRS or the CETP PRS and the risk of adverse sepsis outcomes.

BPOZ-2 is a negative regulator of the NLPR3 inflammasome contributing to SARS-CoV-2-induced hyperinflammation.

Introduction: Inflammation play important roles in the initiation and progression of acute lung injury (ALI), acute respiratory distress syndrome (ARDS), septic shock, clotting dysfunction, or even death associated with SARS-CoV-2 infection. However, the pathogenic mechanisms underlying SARS-CoV-2-induced hyperinflammation are still largely unknown. Methods: The animal model of septic shock and ALI was established after LPS intraperitoneal injection or intratracheal instillation. Bone marrow-derived macrophages (BMDMs) from WT and BPOZ-2 KO mouse strains were harvested from the femurs and tibias of mice. Immunohistology staining, ELISA assay, coimmunoprecipitation, and immunoblot analysis were used to detect the histopathological changes of lung tissues and the expression of inflammatory factors and protein interaction. Results and conclusions: We show a distinct mechanism by which the SARS-CoV-2 N (SARS-2-N) protein targets Bood POZ-containing gene type 2 (BPOZ-2), a scaffold protein for the E3 ubiquitin ligase Cullin 3 that we identified as a negative regulator of inflammatory responses, to promote NLRP3 inflammasome activation. We first demonstrated that BPOZ-2 knockout (BPOZ-2 KO) mice were more susceptible to lipopolysaccharide (LPS)-induced septic shock and ALI and showed increased serum IL-1ß levels. In addition, BMDMs isolated from BPOZ-2 KO mice showed increased IL-1ß production in response to NLRP3 stimuli. Mechanistically, BPOZ-2 interacted with NLRP3 and mediated its degradation by recruiting Cullin 3. In particular, the expression of BPOZ-2 was significantly reduced in lung tissues from mice infected with SARS-CoV-2 and in cells overexpressing SARS-2-N. Importantly, proinflammatory responses triggered by the SARS-2-N were significantly blocked by BPOZ-2 reintroduction. Thus, we concluded that BPOZ-2 is a negative regulator of the NLPR3 inflammasome that likely contributes to SARS-CoV-2-induced hyperinflammation.

Comparison of Characteristics and Outcomes of Multisystem Inflammatory Syndrome, Kawasaki Disease and Toxic Shock Syndrome in Children.

Background and Objectives: Since the first cases of multisystem inflammatory syndrome in children (MIS-C) in April 2020, the diagnostic challenge has been to recognize this syndrome and to differentiate it from other clinically similar pathologies such as Kawasaki disease (KD) and toxic shock syndrome (TSS). Our objective is to compare clinical signs, laboratory data and instrumental investigations between patients with MIS-C, KD and TSS. Materials and Methods: This retrospective observational study was conducted at the Children's Clinical University Hospital, Latvia (CCUH). We collected data from all pediatric patients <18 years of age, who met the Centers for Disease Control and Prevention case definition for MIS-C, and who presented to CCUH between December 2020 and December 2021. We also retrospectively reviewed data from inpatient medical records of patients <18 years of age diagnosed as having KD and TSS at CCUH between December 2015 and December 2021. Results: In total, 81 patients were included in this study: 39 (48.1%) with KD, 29 (35.8%) with MIS-C and 13 (16.1%) with TSS. In comparison with TSS and KD, patients with MIS-C more often presented with gastrointestinal symptoms (abdominal pain (p < 0.001), diarrhea (p = 0.003)), shortness of breath (p < 0.02) and headache (p < 0.003). All MIS-C patients had cardiovascular involvement and 93.1% of MIS-C patients fulfilled KD criteria, showing higher prevalence than in other research. Patients with KD had higher prevalence of cervical lymphadenopathy (p < 0.006) and arthralgias (p < 0.001). In comparison with KD and TSS, MIS-C patients had higher levels of ferritin (p < 0.001), fibrinogen (p = 0.04) and cardiac biomarkers, but lower levels of platelets and lymphocytes (p < 0.001). KD patients tended to have lower peak C-reactive protein (CRP) (p < 0.001), but higher levels of platelets. Acute kidney injury was more often observed in TSS patients (p = 0.01). Pathological changes in electrocardiography (ECG) and echocardiography were significantly more often observed in MIS-C patients (p < 0.001). Conclusions: This research shows that MIS-C, KD and TSS have several clinical similarities and additional investigations are required for reaching final diagnosis. All the patients with suspected MIS-C diagnosis should be examined for possible cardiovascular involvement including cardiac biomarkers, ECG and echocardiography.

Impact of COVID-19 Infection on the Clinical Outcomes of Pulmonary Embolism Hospitalizations : A Nationwide Analysis.

There is an increased risk of venous thromboembolism among patients with COVID-19 infection, with the risk being higher among those needing the intensive level of care. Existing data is, however, limited regarding the outcomes of patients admitted with concurrent COVID-19 infection and pulmonary embolism (PE). All acute PE admissions were identified from the National Inpatient Sample database during 2020 using ICD-10 codes. Patients were subsequently classified into those with and without COVID-19 infection. The primary outcome of interest was in-hospital mortality. Using multivariate logistic regression, the predictors of mortality were assessed for patients with concurrent acute PE and COVID-19. The database query generated 278,840 adult patients with a primary diagnosis of PE. Of these, 4580 patients had concurrent PE and COVID-19 infection. The concurrent PE and COVID-19 infection group had a higher proportion of Black-American and Hispanic patients, and those living in the zip codes associated with the lowest annualized income compared to the PE alone group. Furthermore, patients in the concurrent PE and COVID-19 infection group had an increased risk of in-hospital mortality (adjusted odds ratio [aOR]:1.62; 95% CI: 1.17-2.24; P = 0.004), septic shock (aOR: 1.66; 95% CI 1.10-2.52; P = 0.016), respiratory failure (aOR: 1.78; 95% CI 1.53-2.06; P = 0.001), and a longer hospital stay [5.5 days vs 4.59 days; P = 0.001). Concurrent COVID-19 and PE admissions is associated with an increased in-hospital mortality, risk of septic shock and respiratory failure, and a longer length of hospital stay.

Rationale for sequential extracorporeal therapy (SET) in sepsis.

Sepsis and septic shock remain drivers for morbidity and mortality in critical illness. The clinical picture of patients presenting with these syndromes evolves rapidly and may be characterised by: (a) microbial host invasion, (b) establishment of an infection focus, (c) opsonisation of bacterial products (e.g. lipopolysaccharide), (d) recognition of pathogens resulting in an immune response, (e) cellular and humoral effects of circulating pathogen and pathogen products, (f) immunodysregulation and endocrine effects of cytokines, (g) endothelial and organ damage, and (h) organ crosstalk and multiple organ dysfunction. Each step may be a potential target for a specific therapeutic approach. At various stages, extracorporeal therapies may target circulating molecules for removal. In sequence, we could consider: (a) pathogen removal from the circulation with affinity binders and cartridges (specific), (b) circulating endotoxin removal by haemoperfusion with polymyxin B adsorbers (specific), (c) cytokine removal by haemoperfusion with sorbent cartridges or adsorbing membranes (non-specific), (d) extracorporeal organ support with different techniques for respiratory and cardiac support (CO2 removal or extracorporeal membrane oxygenation), and renal support (haemofiltration, haemodialysis, or ultrafiltration). The sequence of events and the use of different techniques at different points for specific targets will likely require trials with endpoints other than mortality. Instead, the primary objectives should be to achieve the desired action by using extracorporeal therapy at a specific point.