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Sepsis manifests as a dysregulated immune response to an infection, leading to tissue damage, organ failure, and potentially death or long-term health issues. Sepsis remains a major health challenge globally, causing approximately 50 million cases and 11 million deaths annually. Early management of sepsis focuses on source control, antimicrobial treatment, and supporting vital organ function. Subsequent care includes metabolic, nutritional, and immune therapies to address the complex needs of septic patients. Metabolic management is based on obtaining moderate glucose targets. Nutritional support aims to mitigate hypercatabolism and muscle wasting, but aggressive early nutrition does not improve outcomes and could even be harmful. Immune modulation is crucial due to the dual nature of sepsis-induced immune responses. Corticosteroids have shown benefits in shock and organ dysfunction reversal and in mortality reduction with current guidelines recommending them in vasopressor therapy-dependent patients. In conclusion, sepsis management beyond the initial hours requires a multifaceted approach, focusing on metabolic, nutritional, and immune system support tailored to individual patient needs to enhance survival and recovery. [ABSTRACT FROM AUTHOR]

Here we review the epidemiology of sepsis, focusing on its definition, incidence, and mortality, as well as the demographic insights and risk factors that influence its occurrence and outcomes. We address how age, sex, and racial/ethnic disparities impact upon incidence and mortality rates. Sepsis is more frequent and severe among the elderly, males, and certain racial and ethnic groups. Poor socioeconomic status, geographic location, and pre-existing comorbidities also elevate the risk of developing and dying from sepsis. Seasonal variations, with an increased incidence during winter months, is also apparent. We delve into the predictive value of disease severity scores such as the Sequential Organ Failure Assessment score. We also highlight issues relating to coding and administrative data that can generate erroneous and misleading information, and the need for greater consistency. The Sepsis-3 definitions, offering more precise clinical criteria, are a step in the right direction. This overview will, we hope, facilitate understanding of the multi-faceted epidemiological characteristics of sepsis and current challenges. [ABSTRACT FROM AUTHOR]

Leaving university I started working for the Belgian National Radio as a journalist. I used to travel a lot and produce radio features about life abroad and how people all over the world dealt with the different challenges in society. A privileged job that I enjoyed doing for many years. In the meantime, I got married and became a mother of two sons. Nothing to worry about, so it seemed, until January 30, 2009. I had been fighting the symptoms of flu for some days. Instead of recovering, I began to feel worse and worse: I had a high fever, was asleep most of the time, could barely eat or drink, and had to cough a lot. The general practitioner sent me to hospital. A few hours later, I had to be reanimated. It was a close call: I was infected by the Streptococcus pyogenes bacteria. My blood started thickening, my organs stopped functioning, and I went into a septic shock, followed by a cardiac arrest. I was successfully reanimated, but still not stable. For 10 days, I was fighting to survive at the intensive care unit (ICU), with several cardiac arrests and reanimations, some of which were long-lasting. The Head of the ICU informed my husband that there was less than 5% chance to survive and if so, he could not predict what kind of damage there would be: the amount of drugs that I had been given, including noradrenaline, was so extremely high, that it became very unclear how my body would respond to it. And if, as by miracle, I would survive: what kind of damage would there be? Physical? Mental? Physical and mental? No specialist could answer those questions. But both the health care professionals and my family fought to keep me alive. [ABSTRACT FROM AUTHOR]

Sepsis is a medical emergency resulting from a dysregulated response to an infection, causing preventable deaths and a high burden of morbidity. Protocolized and accurate interventions in sepsis are time-critical. Therefore, earlier recognition of cases allows for preventive interventions, early treatment, and improved outcomes. Clinical diagnosis of sepsis by clinical scores cannot be considered an early diagnosis, given that underlying molecular pathophysiological mechanisms have been activated in the preceding hour or days. There is a lack of a widely available tool enhancing preclinical diagnosis of sepsis. Sophisticated technologies for sepsis prediction have several limitations, including high costs. Novel technologies for fast molecular and microbiological diagnosis are focusing on bedside point-of-care combined testing to reach most settings where sepsis represents a challenge. [ABSTRACT FROM AUTHOR]

The objective of this study was to report our cases of spontaneous pyometra perforation and to do a literature review for the same. Total 62 articles were reviewed from the year 2000 to 2023. After detailed screening, a total of 45 cases were selected for review. Analysis was done in terms of age, symptoms, preoperative diagnosis and treatment mainly. The mean age of presentation for SPP is 73 years. Most common presenting symptom is abdominal pain associated with vomiting. The most common preoperative diagnosis for them is hollow viscus perforation i.e., almost 49%. Most common site of rupture has been found to be fundus (71%). Hysterectomy remains the mainstay of treatment. An elderly lady presenting in emergency room with features of frank pyoperitoneum and septic shock, differential of pyometra perforation should always be kept in mind. An early intervention from gynecology department in these patients carries a good prognosis. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening condition but predicting its development and progression remains a challenge. This study aimed to assess the impact of infection site on sepsis development among emergency department (ED) patients. Data were collected from a single-center ED between January 2016 and December 2019. Patient encounters with documented infections, as defined by the Systematized Nomenclature of Medicine-Clinical Terms for upper respiratory tract (URI), lower respiratory tract (LRI), urinary tract (UTI), or skin or soft-tissue infections were included. Primary outcome was the development of sepsis or septic shock, as defined by Sepsis-1/2 criteria. Secondary outcomes included hospital disposition and length of stay, blood and urine culture positivity, antibiotic administration, vasopressor use, in-hospital mortality, and 30-day mortality. Analysis of variance and various different logistic regression approaches were used for analysis with URI used as the reference variable. LRI was most associated with sepsis (relative risk ratio [RRR] 5.63; 95% CI 5.07–6.24) and septic shock (RRR 21.2; 95% CI 17.99–24.98) development, as well as hospital admission rates (odds ratio [OR] 8.23; 95% CI 7.41–9.14), intensive care unit admission (OR 4.27; 95% CI 3.84–4.74), in-hospital mortality (OR 6.93; 95% CI 5.60–8.57), and 30-day mortality (OR 7.34; 95% CI 5.86–9.19). UTIs were also associated with sepsis and septic shock development, but to a lesser degree than LRI. Primary infection sites including LRI and UTI were significantly associated with sepsis development, hospitalization, length of stay, and mortality among patients presenting with infections in the ED. [ABSTRACT FROM AUTHOR]

Background: Septic patients with persistent lymphopenia may be in an immunosuppressed state. Therefore, we evaluated and compared the clinical characteristics and outcomes of septic patients with persistent lymphopenia (≥2d) and those with nonpersistent lymphopenia. Methods: A retrospective cohort study was designed. A total of 1306 patients with sepsis who were attended to the First Affiliated Hospital of Dalian Medical University from March 2016 to August 2022 were included. The primary clinical outcome was 90d mortality. The secondary clinical outcomes were the length of stay, hospital mortality, 28d mortality, the incidence of secondary infection, and differences in clinical characteristics. Results: Among 1306 patients with sepsis, 913 (69.9%) patients developed persistent lymphopenia. Compared with patients with nonpersistent lymphopenia, patients with persistent lymphocytopenia were admitted to intensive care unit (75.7% vs 52.7%, P <.05), treated with mechanical ventilation (67.6% vs 39.2%, P <.05), positive rate of microbial culture pathogens (86.7% vs 71.2%, P <.05), SOFA [8.0 (6.0-10.0) vs 6.0 (4.0-8.0), P <.05], length of stay [17.0d (12.0-27.0) vs 13.0d (10.0-21.0), P <.05], hospital mortality (37.7% vs 24.2%, P <.05), 28d mortality (38.0% vs 22.9%, P <.05), and 90d mortality (51.2% vs 31.3%, P <.05) were higher. As the duration of lymphocytopenia increased, so did the mortality rate in hospital. In addition, the onset time of persistent lymphopenia was not associated with SOFA. But we found that the frequency of persistent lymphopenia during hospitalization was positively associated with SOFA. Conclusion: Septic patients with persistent lymphopenia have higher mortality, worse conditions, increased risk of secondary infection, and poor prognosis regardless of shock. [ABSTRACT FROM AUTHOR]

Background: Sepsis is a serious complication that occurs after trauma, burns, and infections, and it is an important cause of death in intensive care unit (ICU) patients. Despite many new measures being proposed for sepsis treatment, its mortality rate remains high; sepsis has become a serious threat to human health, and there is an urgent need to carry out in-depth clinical research related to sepsis. In recent years, it has been found that septic shock-induced vasoplegia is a result of vascular hyporesponsiveness to vasopressors. Therefore, this study intended to establish an objective formula related to vasoplegia that can be used to assess the prognosis of patients and guide clinical treatment. Materials and Methods: A retrospective cohort study was conducted using data from 106 septic shock patients admitted to the ICU of Jining No. 1 People's Hospital from January 2020 to December 2022. The patients were divided into mortality and survival groups based on 28-day survival, and hemodynamics were monitored by the pulse index continuous cardiac output system. The dose and duration of vasopressors, major hemodynamic parameters, lactic acid (Lac) levels, and Sequential Organ Failure Assessment scores were recorded within 48 h of hospital admission. Multifactorial logistic regression was used to analyze the independent risk factors affecting the prognosis of patients, and the predictive value of the vascular response index (VRI) was analyzed by the receiver operating characteristic (ROC) curve. Results: The differences between the survival and mortality groups in terms of age, sex ratio, body weight, ICU length of stay, distribution of infection sites, underlying disease conditions, baseline Lac levels, and some hemodynamic parameters were not statistically significant (P >.05). The results of multifactorial logistic regression showed that the admission Acute Physiology and Chronic Health Evaluation II score, Lac level at 24 h of treatment, maximal vasoactive inotropic score at 24 h (VISmax24), maximal vasoactive inotropic score at 48 h (VISmax48), and VRI were independent risk factors affecting 28-day mortality. Within 48 h of receiving vasopressor therapy, the VRI was lower in the mortality group than in the survival group. The area under the ROC curve for the VRI was 0.86, and the best cutoff value of the VRI for predicting 28-day mortality was 32.50 (YI = 0.80), with a sensitivity of 0.90, a specificity of 0.90, and a better prediction of mortality than the other indicators. Conclusions: The VRI is a good predictor of mortality in patients with septic shock, and a lower VRI indicates more severe vasoplegia, poorer prognosis, and higher mortality in patients with septic shock. [ABSTRACT FROM AUTHOR]

Alkaline phosphatase (ALP) is an enzyme which has been proven useful as a biomarker for bone turnover and inflammation. We hypothesized that high serum ALP levels are associated with increased complication rates following lumbar spinal fusion. Lumbar spinal fusion procedures from 2005 to 2019 were queried from the National Surgical Quality Improvement Program (NSQIP) database. Serum alkaline phosphatase levels were stratified into low <44 IU/L, normal 44–147 IU/L, and high >147 IU/L. A risk-adjusted multivariate logistic regression was used to analyze ALP as an independent risk factor for complications. A total of 16,441 patients who underwent lumbar fusion procedures were included. Adjusted multivariate logistic regression analysis demonstrated that patients with a high serum ALP level had a significantly increased risk for developing septic shock (OR 4.68, 95% CI 1.83–11.97), pneumonia (OR 2.89, 95% CI 1.59–5.25), requiring a transfusion (OR 2.09, 95% CI 1.68–2.59), reoperation within 30 days (OR 1.68, 95% CI 1.12–2.52), readmission within 30 days (OR 1.60, 95% CI 1.16–2.21), increased length of stay (OR 1.87, 95% CI 1.49–2.36), and nonhome discharge (OR 2.18, 95% CI 1.80–2.66). Elevated serum ALP in patients undergoing lumbar fusion procedures is associated with increased risk for multiple in-hospital complications as well as higher rates of readmission and reoperation. [ABSTRACT FROM AUTHOR]

Small, portable hand-held ultrasound devices nowadays enable a widespread use of prehospital point-of-care ultrasound (pPOCUS), which has so far only been used hesitantly, especially in ground-based emergency services. Many critical or even life-threatening conditions or internal injuries can often be better diagnosed or ruled out using pPOCUS, which can enable faster and more suitable goal-directed treatment and hospital transport. This article critically discusses relevant data, clinical benefits, limitations and challenges to be overcome when using pPOCUS for the most important life-threatening situations and aims to call for intensifying training and the extensive use of pPOCUS. [ABSTRACT FROM AUTHOR]

Disparate and rapidly changing practice recommendations from major professional infectious diseases societies for managing non-severe infections caused by extended-spectrum β-lactamase-producing Enterobacterales might hamper carbapenem stewardship. We aimed to understand the real-world management of extended-spectrum cephalosporin-resistant (ECR) Enterobacterales infections in US hospitals and factors influencing preference for carbapenems over alternative treatments. This retrospective cohort study included adults (aged ≥18 years) admitted to hospital with ECR Enterobacterales infections in the PINC AI database. Antibiotic regimens were assessed during empirical and targeted treatment periods and by infection severity and site. Likelihood of receiving targeted carbapenems over time and before or after initial release of the Infectious Diseases Society of America (IDSA) guidance on Sept 8, 2020, was established with generalised estimating equations controlling for patient, hospital, and temporal confounders. Between Jan 1, 2018, and Dec 31, 2021, 30 041 inpatient encounters with ECR Enterobacterales infections were identified at 168 US hospitals, of which 16 006 (53·3%) encounters were in women and 14 035 (46·7%) were in men, with a mean age of 67·3 years (SD 15·1). Although few patients received carbapenems empirically (5324 [17·7%] of 30 041), many did so as targeted treatment (17 518 [58·3%] of 30 041), including subgroups of patients without septic shock (3031 [45·6%] of 6651) and patients with urinary tract infections without septic shock (1845 [46·8%] of 3943) in whom specific narrower-spectrum alternatives were active. Transitions from non-carbapenem to carbapenem antibiotics occurred most often on the day that the ECR phenotype was reported, regardless of illness severity. Carbapenems were the predominant choice to treat ECR Enterobacterales infections over time (adjusted odds ratio 1·00 [95% CI 1·00–1·00]), with no additional immediate change (1·07 [0·95–1·20]) or sustained change (0·99 [0·98–1·00]) after IDSA guidance release. High carbapenem use in targeting non-severe ECR Enterobacterales infections in US hospitals predates 2020 IDSA guidance and has persisted thereafter. Efforts to increase awareness and implementation of recommendations among clinicians to use carbapenem-sparing alternatives in ECR Enterobacterales infections might decrease global carbapenem selective pressure. US National Institutes of Health Intramural Research Program, National Institute of Allergy and Infectious Diseases, and US Food and Drug Administration. [ABSTRACT FROM AUTHOR]

Summary: Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta‐analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all‐cause mortality. Fifty‐six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti‐inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1‐month follow‐up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events, based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90–1.00), I2 = 0%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll‐like receptor 4 antagonists (RR (95%CI) 1.18 (1.04–1.34), I2 = 0% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1‐month mortality (RR (95%CI) 0.88 (0.78–0.98), I2 = 57%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti‐tumour necrosis factor α interventions (RR (95%CI) 0.93 (0.87–0.99), I2 = 0%). Anti‐inflammatory drugs had the largest apparent effect on mortality at 2 months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51–0.80), I2 = 0%) and at 3 months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55–0.81), I2 = 0%). These data indicate that, except for toll‐like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short‐term mortality benefit for selected drugs. [ABSTRACT FROM AUTHOR]

Background: Polymyxins have re‐emerged as a last‐resort therapeutic option for infections caused by carbapenem‐resistant gram‐negative bacteria. Nephrotoxicity induced by polymyxins is a significant limitation of its use in the clinic. Polymyxin B and colistin sulfate are two widely used active formulations of polymyxins. However, there is a lack of studies conducting a comparative assessment of nephrotoxicity between the two formulations. This study aimed to compare the nephrotoxicity of polymyxin B and colistin sulfate in critically ill patients. Methods: We conducted a retrospective cohort study among critically ill patients who received intravenous polymyxin B or colistin sulfate for over 48 h from January 2017 to January 2024. The primary outcome was the incidence of acute kidney injury (AKI) associated with polymyxins, and the secondary outcome was 30‐day all‐cause mortality. Additionally, the risk factors of polymyxins‐induced AKI and 30‐day all‐cause mortality were identified by Cox proportional hazard regression analysis. Results: A total of 473 patients were included in this study. The overall incidence of AKI was significantly higher in patients who received polymyxin B compared to those who received colistin sulfate in the unmatched cohort (20.8% vs. 9.0%, p = 0.002) and in the propensity score matching cohort (21.1% vs. 7.0%, p = 0.004), respectively. However, there was no significant difference in 30‐day all‐cause mortality between the two groups. Polymyxin type, septic shock, and concomitant use of vasopressors were identified as independent risk factors for polymyxin‐induced AKI. Conclusions: The prevalence of AKI was higher among patients who received polymyxin B compared to those treated with colistin sulfate. However, there was no significant difference in 30‐day all‐cause mortality between the two groups. Further prospective, multicenter studies with larger sample sizes are needed to validate these findings. [ABSTRACT FROM AUTHOR]

Objective: To describe clinical, laboratory, and antibiotic treatment characteristics in pregnant or recently pregnant women diagnosed with maternal sepsis. Methods: A retrospective cohort study was conducted in a Brazilian tertiary hospital from March 2014 until February 2018. The hospital implemented a Sepsis Protocol, based on the Brazilian Ministry of Health recommendation. All women who were pregnant or recently pregnant (up to 42 days postpartum), and who presented with suspected sepsis were included. Unconfirmed infections were excluded. Three hundred sixty‐five women were included and divided into three groups according to sepsis severity (SEPSIS‐2): sepsis, severe sepsis, and septic shock. Clinical, laboratory, and management characteristics were described and compared. Results: Pregnancy‐related and respiratory tract infections were the greater causes of maternal sepsis, and the urinary tract was the major cause of septic shock. We found almost total compliance with blood culture sample collection, and samples were positive in 10.8% of the cases, and in 41% of septic shock patients. Escherichia coli was the most common pathogen found and it was resistant to third‐generation cephalosporins in none of the blood cultures and 3.3% of the urine cultures. Using the AWaRe (Access, Watch and Reserve) classification groups of antibiotics, Access and Watch antibiotics were used in virtually all women. We did not find any fatal maternal outcomes. Conclusion: Maternal sepsis is seldom the result of resistant microorganisms in this setting and the use of Access group antibiotics is widely possible. Health professionals' awareness of and institutional policies for maternal sepsis are crucial to its adequate treatment and better outcomes. Synopsis: A protocol for maternal sepsis to be routinely used is able to provide better treatment and improve outcomes reducing infectious complications. [ABSTRACT FROM AUTHOR]

Due to the high morbidity associated with esophagectomies, patients are often directly admitted to intensive care units (ICUs) for postoperative monitoring. However, critical complications can arise after this initial ICU stay. We hypothesized that the timing of ICU stay was not optimal for the care of patients after esophagectomy and aimed to determine when patients are at risk for developing critical complications. We searched the National Safety and Quality Improvement Program for patients who underwent an esophagectomy between 2016 and 2021. The outcome of interest was the interval between surgery and first critical complication. A critical complication was defined as one likely to require intensive care, including respiratory failure, septic shock, etc. Multivariate regression was performed to identify the risks of complications. This study included 6813 patients from more than 70 institutions. Within the first 30 d postesophagectomy, 21.59% of patients experienced at least one critical complication. Half of first critical complications occurred after postoperative day 5, and 85.05% of them occurred after postoperative day 2. Risk factors for critical complications included age greater than 60 y, preoperative comorbidities, and open surgical approach. Malignancies were associated with a significantly lower incidence of critical complications. Critical complications occurred beyond the immediate postesophagectomy period. Therefore, low-risk patients undergoing minimally invasive esophagectomies can be safely monitored outside the ICU, allowing for better patient care and resource utilization. • The majority of first critical complications occur after day two postesophagectomy. • Preoperative patient characteristics are associated with critical complications. • Neoadjuvant treatment does not increase the risk of postesophagectomy morbidity. • Indiscriminate ICU admission overtriages low risk postesophagectomy patients. [ABSTRACT FROM AUTHOR]

Systemic inflammatory response syndrome (SIRS) is an uncontrolled systemic inflammatory response. Proanthocyanidins (PC) is a general term of polyphenol compounds widely existed in blueberry fruits and can treat inflammation-related diseases. This study aimed to explore the regulatory effect of PC on lipopolysaccharide (LPS)-induced systemic inflammation and its potential mechanism, providing effective strategies for the further development of PC. Here, RAW264.7 macrophages were stimulated with LPS to establish an inflammation model in vitro, while endotoxin shock mouse models were constructed by LPS in vivo. The function of PC was investigated by MTT, ELISA kits, H&E staining, immunohistochemistry, and Western blot analysis. Functionally, PC could demonstrate the potential to mitigate mortality in mice with endotoxin shock, as well as attenuated the levels of inflammatory cytokines (IL-6, TNF-α) and biochemical indicators (AST, ALT, CRE and BUN). Moreover, it had a significant protective effect on lung and kidney tissues damage. Mechanistically, PC exerted anti-inflammatory effects by inhibiting the activation of the NF-κB/NLRP3 signaling pathway. PC might have the potential ability of anti-inflammatory effects via modulation of the NF-κB/NLRP3 signaling pathway. [ABSTRACT FROM AUTHOR]

The acute manifestations of coronavirus disease 2019 (COVID-19) exhibit the hallmarks of sepsis-associated complications that reflect multiple organ failure. The inflammatory cytokine storm accompanied by an imbalance in the pro-inflammatory and anti-inflammatory host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to severe and critical septic shock. The sepsis signature in severely afflicted COVID-19 patients includes cellular reprogramming and organ dysfunction that leads to high mortality rates, emphasizing the importance of improved clinical care and advanced therapeutic interventions for sepsis associated with COVID-19. Phytochemicals of functional foods and nutraceutical importance have an incredible impact on the healthcare system, which includes the prevention and/or treatment of chronic diseases. Hence, in the present review, we aim to explore the pathogenesis of sepsis associated with COVID-19 that disrupts the physiological homeostasis of the body, resulting in severe organ damage. Furthermore, we have summarized the diverse pharmacological properties of some potent phytochemicals, which can be used as functional foods as well as nutraceuticals against sepsis-associated complications of SARS-CoV-2 infection. The phytochemicals explored in this article include quercetin, curcumin, luteolin, apigenin, resveratrol, and naringenin, which are the major phytoconstituents of our daily food intake. We have compiled the findings from various studies, including clinical trials in humans, to explore more into the therapeutic potential of each phytochemical against sepsis and COVID-19, which highlights their possible importance in sepsis-associated COVID-19 pathogenesis. We conclude that our review will open a new research avenue for exploring phytochemical-derived therapeutic agents for preventing or treating the life-threatening complications of sepsis associated with COVID-19. [ABSTRACT FROM AUTHOR]

The autonomic nervous system plays a key role in maintaining body hemostasis through both the sympathetic and parasympathetic nervous systems. Sympathetic overstimulation as a reflex to multiple pathologies, such as septic shock, brain injury, cardiogenic shock, and cardiac arrest, could be harmful and lead to autonomic and immunologic dysfunction. The continuous stimulation of the beta receptors on immune cells has an inhibitory effect on these cells and may lead to immunologic dysfunction through enhancing the production of anti-inflammatory cytokines, such as interleukin-10 (IL-10), and inhibiting the production of pro-inflammatory factors, such as interleukin-1B IL-1B and tissue necrotizing factor-alpha (TNF-alpha). Sympathetic overstimulation-induced autonomic dysfunction may also happen due to adrenergic receptor insensitivity or downregulation. Administering anti-adrenergic medication, such as beta-blockers, is a promising treatment to compensate against the undesired effects of adrenergic surge. Despite many misconceptions about beta-blockers, beta-blockers have shown a promising effect in decreasing mortality in patients with critical illness. In this review, we summarize the recently published articles that have discussed using beta-blockers as a promising treatment to decrease mortality in critically ill patients, such as patients with septic shock, traumatic brain injury, cardiogenic shock, acute decompensated heart failure, and electrical storm. We also discuss the potential pathophysiology of beta-blockers in various types of critical illness. More clinical trials are encouraged to evaluate the safety and effectiveness of beta-blockers in improving mortality among critically ill patients. [ABSTRACT FROM AUTHOR]

Objectives Polymyxin-induced nephrotoxicity (PIN) is a major safety concern and challenge in clinical practice, which limits the clinical use of polymyxins. This study aims to investigate the risk factors and to develop a scoring tool for the early prediction of PIN. Methods Data on critically ill patients who received intravenous polymyxin B or colistin sulfate for over 24 h were collected. Logistic regression with the least absolute shrinkage and selection operator (LASSO) was used to identify variables that are associated with outcomes. The eXtreme Gradient Boosting (XGB) classifier algorithm was used to further visualize factors with significant differences. A prediction model for PIN was developed through binary logistic regression analysis and the model was assessed by temporal validation and external validation. Finally, a risk-scoring system was developed based on the prediction model. Results Of 508 patients, 161 (31.6%) patients developed PIN. Polymyxin type, loading dose, septic shock, concomitant vasopressors and baseline blood urea nitrogen (BUN) level were identified as significant predictors of PIN. All validation exhibited great discrimination, with the AUC of 0.742 (95% CI: 0.696–0.787) for internal validation, of 0.708 (95% CI: 0.605–0.810) for temporal validation and of 0.874 (95% CI: 0.759–0.989) for external validation, respectively. A simple risk-scoring tool was developed with a total risk score ranging from −3 to 4, corresponding to a risk of PIN from 0.79% to 81.24%. Conclusions This study established a prediction model for PIN. Before using polymyxins, the simple risk-scoring tool can effectively identify patients at risk of developing PIN within a range of 7% to 65%. [ABSTRACT FROM AUTHOR]

OBJECTIVES: In 2018, the Centers for Disease Control and Prevention introduced the Adult Sepsis Event (ASE) definition, using electronic health records (EHRs) data for surveillance and sepsis quality improvement. However, data regarding ASE outside the United States remain limited. We therefore aimed to validate the diagnostic accuracy of the ASE and to assess the prevalence and mortality of sepsis using ASE. DESIGN: Retrospective cohort study. SETTING: A single center in South Korea, with 2732 beds including 221 ICU beds. PATIENTS: During the validation phase, adult patients who were hospitalized or visiting the emergency department between November 5 and November 11, 2019, were included. In the subsequent phase of epidemiologic analysis, we included adult patients who were admitted from January to December 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ASE had a sensitivity of 91.6%, a specificity of 98.3%, a positive predictive value (PPV) of 57.4%, and a negative predictive value of 99.8% when compared with the Sepsis-3 definition. Of 126,998 adult patient hospitalizations in 2020, 6,872 cases were diagnosed with sepsis based on the ASE (5.4% per year), and 893 patients were identified as having sepsis according to the International Classification of Diseases, 10th Edition (ICD-10) (0.7% per year). Hospital mortality rates were 16.6% (ASE) and 23.5% (ICD-10-coded sepsis). Monthly sepsis prevalence and hospital mortality exhibited less variation when diagnosed using ASE compared with ICD-10 coding (coefficient of variation [CV] for sepsis prevalence: 0.051 vs. 0.163, Miller test p < 0.001; CV for hospital mortality: 0.087 vs. 0.261, p = 0.001). CONCLUSIONS: ASE demonstrated high sensitivity and a moderate PPV compared with the Sepsis-3 criteria in a Korean population. The prevalence of sepsis, as defined by ASE, was 5.4% per year and was similar to U.S. estimates. The prevalence of sepsis by ASE was eight times higher and exhibited less monthly variability compared with that based on the ICD-10 code. [ABSTRACT FROM AUTHOR]

This article discusses the challenges of accurately measuring the incidence and mortality of sepsis, a global health priority. The U.S. Centers for Disease Control and Prevention (CDC) developed the "Adult Sepsis Event" (ASE) definition in 2018, which uses clinical data from electronic health records (EHR) to identify sepsis. This study in South Korea validates the feasibility and benefits of using the ASE definition to measure sepsis incidence and outcomes outside of the U.S. The study also highlights the limitations of using International Classification of Diseases (ICD) codes for tracking sepsis. The findings suggest that ASE surveillance could facilitate standardized international comparisons of sepsis rates and mortality. The study identifies areas for improvement, such as incorporating additional criteria and improving the match between electronic and traditional assessment methods. However, the study's limitations include its focus on a single hospital and a single year during the COVID-19 pandemic. The authors emphasize the importance of conducting sepsis surveillance in low- and middle-income settings and the potential for ASE surveillance to provide reliable global data on sepsis epidemiology. [Extracted from the article]

OBJECTIVES: Some studies have examined survival trends among critically ill COVID-19 patients, but most were case reports, small cohorts, and had relatively short follow-up periods. We aimed to examine the survival trend among critically ill COVID-19 patients during the first two and a half years of the pandemic and investigate potential predictors across different variants of concern periods. DESIGN: Prospective cohort study. SETTING: Swedish ICUs, between March 6, 2020, and December 31, 2022. PATIENTS: Adult COVID-19 ICU patients of 18 years old or older from the Swedish Intensive Care Register (SIR) that were linked to multiple other national registers. MEASUREMENT AND MAIN RESULTS: Survival probability and predictors of COVID-19 death were estimated using Kaplan-Meier and Cox regression analysis. Of 8975 patients, 2927 (32.6%) died. The survival rate among COVID-19 critically ill patients appears to have changed over time, with a worse survival in the Omicron period overall. The adjusted hazard ratios (aHRs) comparing older and younger ages were consistently strong but slightly attenuated in the Omicron period. After adjustment, the aHR of death was significantly higher for men, older age (40+ yr), low income, and with comorbid chronic heart disease, chronic lung disease, impaired immune disease, chronic renal disease, stroke, and cancer, and for those requiring invasive or noninvasive respiratory supports, who developed septic shock or had organ failures (p < 0.05). In contrast, foreign-born patients, those with booster vaccine, and those who had taken steroids had better survival (aHR = 0.87; 95% CI, 0.80-0.95; 0.74, 0.65-0.84, and 0.91, 0.84-0.98, respectively). Observed associations were similar across different variant periods. CONCLUSIONS: In this nationwide Swedish cohort covering over two and a half years of the pandemic, ICU survival rates changed over time. Older age was a strong predictor across all periods. Furthermore, most other mortality predictors remained consistent across different variant periods. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Low cholesterol levels in early sepsis patients are associated with mortality. We sought to test if IV lipid emulsion administration to sepsis patients with low cholesterol levels would prevent a decline or increase total cholesterol levels at 48 hours. DESIGN: Phase II, adaptive, randomized pilot clinical trial powered for 48 patients. SETTING: Emergency department or ICU of an academic medical center. PATIENTS: Sepsis patients (first 24 hr) with Sequential Organ Failure Assessment greater than or equal to 4 or shock. INTERVENTIONS: Patients meeting study criteria, including screening total cholesterol levels less than or equal to 100 mg/dL or high-density lipoprotein cho- lesterol (HDL-C) + low-density lipoprotein cholesterol (LDL-C) less than or equal to 70 mg/dL, were randomized to receive one of three doses of lipid emulsion administered twice in 48 hours or no drug (controls). The primary endpoint was a change in serum total cholesterol (48 hr -- enrollment) between groups. MEASUREMENTS AND MAIN RESULTS: Forty-nine patients were enrolled and randomized. Two patients randomized to lipid emulsion were withdrawn before drug administration. Data for 24 control patients and 23 lipid emulsion patients were analyzed. The mean change in total cholesterol from enrollment to 48 hours was not different between groups and was 5 mg/dL (sd 20) for lipid emulsion patients, and 2 mg/dL (sd 18) for control patients (p = 0.62). The mean changes in HDL-C and LDL-C were similar between groups. Mean change in triglycerides was elevated in lipid emulsion patients (61 mg/dL, sd 87) compared with controls (20 mg/dL, sd 70, p = 0.086). The 48-hour change in SOFA score was -2 (interquartile range [IQR] -4, -1) for control patients and -2 (IQR -3, 0) for lipid emulsion patients (p = 0.46). CONCLUSIONS: Administration of IV lipid emulsion to early sepsis patients with low cholesterol levels did not influence change in cholesterol levels from enrollment to 48 hours. [ABSTRACT FROM AUTHOR]

Campylobacter fetus accounts for 1% of Campylobacter spp. infections, but prevalence of bacteremia and risk for death are high. To determine clinical features of C. fetus infections and risks for death, we conducted a retrospective observational study of all adult inpatients with a confirmed C. fetus infection in Nord Franche-Comté Hospital, Trevenans, France, during January 2000-December 2021. Among 991 patients with isolated Campylobacter spp. strains, we identified 39 (4%) with culture-positive C. fetus infections, of which 33 had complete records and underwent further analysis; 21 had documented bacteremia and 12 did not. Secondary localizations were reported for 7 (33%) patients with C. fetus bacteremia, of which 5 exhibited a predilection for vascular infections (including 3 with mycotic aneurysm). Another 7 (33%) patients with C. fetus bacteremia died within 30 days. Significant risk factors associated with death within 30 days were dyspnea, quick sequential organ failure assessment score >2 at admission, and septic shock. [ABSTRACT FROM AUTHOR]

This study aimed to determine the association of Escherichia coli microbiological factors with 30-day mortality in patients with bloodstream infection (BSI) presenting with a dysregulated response to infection (i.e. sepsis or septic shock). Whole-genome sequencing was performed on 224 E coli isolates of patients with sepsis/septic shock, from 22 Spanish hospitals. Phylogroup, sequence type, virulence, antibiotic resistance, and pathogenicity islands were assessed. A multivariable model for 30-day mortality including clinical and epidemiological variables was built, to which microbiological variables were hierarchically added. The predictive capacity of the models was estimated by the area under the receiver operating characteristic curve (AUROC) with 95% confidence intervals (CI). Mortality at day 30 was 31% (69 patients). The clinical model for mortality included (adjusted OR; 95% CI) age (1.04; 1.02–1.07), Charlson index ≥3 (1.78; 0.95–3.32), urinary BSI source (0.30; 0.16–0.57), and active empirical treatment (0.36; 0.11–1.14) with an AUROC of 0.73 (95% CI, 0.67–0.80). Addition of microbiological factors selected clone ST95 (3.64; 0.94–14.04), eilA gene (2.62; 1.14–6.02), and astA gene (2.39; 0.87–6.59) as associated with mortality, with an AUROC of 0.76 (0.69–0.82). Despite having a modest overall contribution, some microbiological factors were associated with increased odds of death and deserve to be studied as potential therapeutic or preventive targets. [ABSTRACT FROM AUTHOR]

Objectives: Sepsis is a systemic inflammatory disorder characterized by life-threateningorgan dysfunction resulting from a dysregulated host response to infection. Prostacyclin (PGI2) is a bioactive lipid produced by PGI synthase (PGIS) and is known to play important roles in inflammatory reactions as well as cardiovascular regulation. However, little is known about the roles of PGIS and PGI2 in systemic inflammatory responses such as septic shock. Methodology: Systemic inflammation was induced by intraperitoneal injection of 5 mg/kg lipopolysaccharide (LPS) in wild type (WT) or PGIS knockout (KO) mice. Selexipag, a selective PGI2 receptor (IP) agonist, was administered 2 h before LPS injection and again given every 12 h for 3 days. Results: Intraperitoneal injection of LPS induced diarrhea, shivering and hypothermia. These symptoms were more severe in PGIS KO mice than in WT micqe. The expression of Tnf and Il6 genes was notably increased in PGIS KO mice. In contrast, over 95% of WT mice survived 72 h after the administration of LPS, whereas all of the PGIS KO mice had succumbed by that time. The mortality rate of LPS-administrated PGIS KO mice was improved by selexipag administration. Conclusion: Our study suggests that PGIS-derived PGI2 negatively regulates LPS-induced symptoms via the IP receptor. PGIS-derived PGI2-IP signaling axis may be a new drug target for systemic inflammation in septic shock. [ABSTRACT FROM AUTHOR]

This document, titled "Empirical antimicrobials in the intensive care unit," provides guidance on prescribing empirical antimicrobial treatment for patients in the intensive care unit (ICU) with suspected infections. The document emphasizes the importance of proper diagnostic assessment, including clinical examination, imaging, and laboratory testing, to determine the need for antimicrobial therapy. It also discusses the urgency of administering antimicrobials promptly in cases of sepsis or septic shock. The document highlights the need for pathogen profiling and selecting the appropriate antimicrobial regimen based on factors such as the severity of illness, presumed source of infection, and risk of multidrug-resistant organisms. It also mentions the importance of considering pharmacokinetic/pharmacodynamic factors and the potential for future advancements in diagnosing sepsis and identifying causative microorganisms. [Extracted from the article]

Guillain-Barré Syndrome (GBS) is a polyneuropathy characterized by acute-onset and immune-mediated processes, triggered by various factors. The occurence of GBS in connection with snakebites is rare. In this report, we present a rare clinical case with neuro-muscular and hematological complications following a snakebite, leading to flask quadriplegia on the 14th day during intensive care follow-up. Cerebrospinal fluid (CSF) analysis indicated albumin-cytological dissociation, and Electromyography (EMG) revealed findings consistent with acute motor axonal neuropathy, resulting in a diagnosis of GBS. After undergoing plasmapheresis once, the patient swiftly developed refractory septic shock, leading to a fatal outcome. In this study, we report a GBS case as a conseqeunce of snakebite together with a systematic review of the medical literature on the development of GBS after snakebite. Although current case reports and findings have broadened the scope of etiologic hypotheses for GBS including snake envenomation, further studies are needed to confirm the association between GBS following snakebite. [ABSTRACT FROM AUTHOR]

Background and Objective: Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal. This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF). Methods: Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cleff) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days. Results: HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (β = − 8.90 (95% CI − 12.9 to − 4.87), p < 0.001) and tazobactam (β = − 8.29 (95% CI − 13.5 to − 3.08), p = 0.002) and Cleff for each antibiotic (meropenem β = − 10,206 (95% CI − 14,787 to − 5787), p = 0.001); tazobactam (β = − 4551 (95% CI − 7781 to − 1322), p = 0.012); piperacillin (β = − 3913 (95% CI − 6388 to − 1437), p = 0.002), even if the carryover effect influenced the Cleff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (β = − 38.1 (95% CI − 47.9 to − 28.3), p < 0.001) and tazobactam (β = − 4.45 (95% CI − 6.17 to − 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type. Conclusion: MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM. [ABSTRACT FROM AUTHOR]

Background: Variation in usual practice in fluid trials assessing lower versus higher volumes may affect overall comparisons. To address this, we will evaluate the effects of heterogeneity in treatment intensity in the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care trial. This will reflect the effects of differences in site‐specific intensities of standard fluid treatment due to local practice preferences while considering participant characteristics. Methods: We will assess the effects of heterogeneity in treatment intensity across one primary (all‐cause mortality) and three secondary outcomes (serious adverse events or reactions, days alive without life support and days alive out of hospital) after 90 days. We will classify sites based on the site‐specific intensity of standard fluid treatment, defined as the mean differences in observed versus predicted intravenous fluid volumes in the first 24 h in the standard‐fluid group while accounting for differences in participant characteristics. Predictions will be made using a machine learning model including 22 baseline predictors using the extreme gradient boosting algorithm. Subsequently, sites will be grouped into fluid treatment intensity subgroups containing at least 100 participants each. Subgroups differences will be assessed using hierarchical Bayesian regression models with weakly informative priors. We will present the full posterior distributions of relative (risk ratios and ratios of means) and absolute differences (risk differences and mean differences) in each subgroup. Discussion: This study will provide data on the effects of heterogeneity in treatment intensity while accounting for patient characteristics in critically ill adult patients with septic shock. Registrations: The European Clinical Trials Database (EudraCT): 2018‐000404‐42, ClinicalTrials. gov: NCT03668236. [ABSTRACT FROM AUTHOR]

Objective: The incidence of sepsis in older adults has been increasing with the general aging of the Japanese population. However, it has been shown that age is a critical factor in determining both the risk for sepsis and subsequent vital outcomes; aggressive treatment is often discouraged in this vulnerable patient group. This study aimed to determine whether aggressive therapeutic interventions were associated with mortality in older Japanese patients experiencing septic shock. Design: Single-center retrospective cohort study. Setting: Medical Intensive Care Unit of a city hospital (Kishiwada Tokushukai Hospital) in Japan between January 2020 and September 2021. Patients: Patients diagnosed with septic shock at the time of admission and older patients over 65 years of age were included and divided into two groups: a withholding group that received only minimal peripheral infusion and antibiotic therapy and a treatment group (non-withholding group) that received intensive care, such as vas- opressor use or mechanical ventilator management. Interventions: None. Measurements and results: One hundred patients were included in this study. There were 13 and 87 patients in the withholding and non-withholding groups, respectively. There was no significant difference in 30-day mortality between the two groups (53.85% vs 39.08%, p=0.127). However, the 72-hour mortality was significantly higher in the withholding group (53.8% vs 25.3%, p=0.034). Conclusions: Among older patients with septic shock, the withholding group showed a survival rate that was not significantly different from that of the non-withholding group. On the other hand, some level of survival may be expected in patients who withhold treatment after 72 hours or more. Further studies are needed to determine the impact of withholding treatment on patients, not only in terms of mortality but also in terms of long-term prognosis and activities of daily living after discharge from the hospital. [ABSTRACT FROM AUTHOR]

Background: Pneumonia is an infectious disease with high mortality rates despite early diagnosis and adequate treatment. Therefore, the use of biological infection parameters is expected to improve patients' clinical outcome prognostic accuracy. In this study, we proposed a combination of decreased procalcitonin (PCT) and C-reactive protein (CRP) to predict the clinical outcome of severe pneumonia. Methods: This was a prospective cohort study of severe pneumonia patients treated in the single-center Intensive Care Unit (ICU) of Dr. Soetomo General Hospital from December 2023 to February 2024. Subjects who met the inclusion and exclusion criteria were examined for PCT and CRP within the first 24 hours of admission and repeated 96 hours later (day five). Clinical outcomes, including acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), septic shock, and 30-day mortality, were observed. Results: Thirty-five patients were enrolled for this study. Five subjects did not survive until the fifth day, and 30 subjects were eligible for analysis. A decrease of PCT >50% within five days was associated with a reduction of 30-day mortality (p=0.013) and septic shock incidence (p=0.005), whereas the decrease in CRP alone did not show any significant relationship towards any clinical outcome. The combination of a decreased PCT >50% and decreased CRP within five days could increase the prognostic specificity up to 88.9% in predicting 30-day mortality. Conclusion: Decreased PCT by more than 50% within 96 hours may predict the 30-day mortality rate and septic shock incidence in patients with severe pneumonia, while combining it with a decreased CRP expression would elevate prognostic specificity for severe pneumonia. [ABSTRACT FROM AUTHOR]

Delirium is common during critical illness and is associated with long-term cognitive impairment and disability. Antipsychotics are frequently used to treat delirium, but their effects on long-term outcomes are unknown. We aimed to investigate the effects of antipsychotic treatment of delirious, critically ill patients on long-term cognitive, functional, psychological, and quality-of-life outcomes. This prespecified, long-term follow-up to the randomised, double-blind, placebo-controlled phase 3 MIND-USA Study was conducted in 16 hospitals throughout the USA. Adults (aged ≥18 years) who had been admitted to an intensive care unit with respiratory failure or septic or cardiogenic shock were eligible for inclusion in the study if they had delirium. Participants were randomly assigned—using a computer-generated, permuted-block randomisation scheme with stratification by trial site and age—in a 1:1:1 ratio to receive intravenous placebo, haloperidol, or ziprasidone for up to 14 days. Investigators and participants were masked to treatment group assignment. 3 months and 12 months after randomisation, we assessed survivors' cognitive, functional, psychological, quality-of-life, and employment outcomes using validated telephone-administered tests and questionnaires. This trial was registered with ClinicalTrials.gov , NCT01211522 , and is complete. Between Dec 7, 2011, and Aug 12, 2017, we screened 20 914 individuals, of whom 566 were eligible and consented or had consent provided to participate. Of these 566 patients, 184 were assigned to the placebo group, 192 to the haloperidol group, and 190 to the ziprasidone group. 1-year survival and follow-up rates were similar between groups. Cognitive impairment was common in all three treatment groups, with a third of survivors impaired at both 3-month and 12-month follow-up in all groups. More than half of the surveyed survivors in each group had cognitive or physical limitations (or both) that precluded employment at both 3-month and 12-month follow-up. At both 3 months and 12 months, neither haloperidol (adjusted odds ratio 1·22 [95% CI 0·73–2.04] at 3 months and 1·12 [0·60–2·11] at 12 months) nor ziprasidone (1·07 [0·59–1·96] at 3 months and 0·94 [0·62–1·44] at 12 months) significantly altered cognitive outcomes, as measured by the Telephone Interview for Cognitive Status T score, compared with placebo. We also found no evidence that functional, psychological, quality-of-life, or employment outcomes improved with haloperidol or ziprasidone compared with placebo. In delirious, critically ill patients, neither haloperidol nor ziprasidone had a significant effect on cognitive, functional, psychological, or quality-of-life outcomes among survivors. Our findings, along with insufficient evidence of short-term benefit and frequent inappropriate continuation of antipsychotics at hospital discharge, indicate that antipsychotics should not be used routinely to treat delirium in critically ill adults. National Institutes of Health and the US Department of Veterans Affairs. [ABSTRACT FROM AUTHOR]

Background: Perianal infection has a high incidence and mortality rate in patients with acute myeloid leukemia (AML). Sometimes there is a lack of effective anti-infective treatment regimens. Case Presentation: A 58-year-old male diagnosed with AML presented with secondary perianal infection and septic shock upon admission. Although multiple pathogen cultivation and antibiotic sensitivity tests indicated the presence of sensitive strains, the corresponding antibiotics were ineffective. As a last resort, carrimycin was introduced, ultimately controlling the infection and leading to disease remission. Conclusion: Carrimycin is a complementary treatment option when conventional antibiotic therapy fails. It operates through multiple mechanisms beyond its antibiotic properties and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: Patients with nasopharyngeal carcinoma (NPC) combined with non-tuberculous Mycobacteria-pulmonary disease (NTM-PD) are very rare in the clinic, and our case is the first patient with NPC combined with NTM-PD. For oncologists, rapid control of the symptoms of infection is essential to the treatment of the primary disease. Case Presentation: A 58-year-old man who developed a NTM-PD after chemotherapy for nasopharyngeal carcinoma. Granulocytosis after chemotherapy is a major factor in the development of various infectious diseases. Nasopharyngeal tumor was found on MRI of the patient's head, and nasopharyngeal malignant tumor was considered after pathological examination after endoscopic resection of intranasal lesion, and then nasopharyngeal non-keratonic carcinoma (T4N1M0, stage IV) was confirmed in the department of oncology. The patient developed bone marrow suppression after chemotherapy and was admitted to hospital due to septic shock. Chest CT examination indicated pulmonary infection, and empirical antibiotic treatment was not effective. The NGS results showed that the patient was infected with Mycobacterium abscess. We treated with cefoxitin followed by moxifloxacin to reduce the lung lesions significantly. Conclusion: NPC with NTM-PD is very rare, and the treatment of NTM-PD is very important for the prognosis of the patient's primary disease. Our study provides experience for anti-infection treatment of patients with immunosuppression. [ABSTRACT FROM AUTHOR]

Sepsis is among the most frequent diagnoses on admission to the intensive care unit (ICU). A systemic inflammatory response, activated by uncontrolled infection, fosters hypoperfusion and multiorgan failure and often leads to septic shock and mortality. These infections arise from a specific anatomic source, and how the infection foci influence the outcomes is unknown. All patients admitted to the ICU of Hospital de Vila Franca de Xira, between 1 January 2017 and 31 June 2023, were screened for sepsis and categorized according to their infection foci. During the study period, 1296 patients (32.2%) had sepsis on admission. Their mean age was 67.5 ± 15.3 and 58.1% were male; 73.0% had community-acquired infections. The lung was the main focus of infection. Septic shock was present in 37.9% of the patients and was associated with hospital mortality. Severe imbalances were noted in its incidence, and there was lower mortality in lung infections. The hospital-acquired infections had a slightly higher mortality but, after adjustment, this difference was non-significant. Patients with secondary bacteremia had a worse prognosis (one-year adjusted hazard ratio of 1.36, 95% confidence interval 1.06–1.74, p = 0.015), especially those with an isolated non-fermenting Gram-negative infection. Lung, skin, and skin structure infections and peritonitis had a worse prognosis, whilst urinary, biliary tract, and other intra-abdominal infections had a better one-year outcome. [ABSTRACT FROM AUTHOR]

This study explores whether Escherichia coli Nissle 1917 (EcN) can preserve the integrity of the intestinal barrier by modulating the metabolism pathway of short-chain fatty acids (SCFAs) in a C57BL/6J mouse model of lipopolysaccharide (LPS)-induced acute enteritis and a model of a Caco-2 monolayer. The study involved establishing a septic shock model in mice through lipopolysaccharide (LPS) injection. Clinical scores and intestinal permeability were meticulously documented. Immunofluorescence was utilized to localize the tight junction proteins. A quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess the expression of G protein-coupled receptors (GPRs) signaling. Additionally, the supplement of acetate and butyrate with Caco-2 monolayers to elucidate the potential of EcN in augmenting the intestinal barrier primarily via the modulation of SCFAs and qRT-PCR was performed to detect the expression of tight junction proteins and the activation of the GPRs protein signaling pathway. EcN mitigated the clinical symptoms and reduced intestinal permeability in the colon of LPS-induced mice. It also enhanced the production of SCFAs in the gut and upregulated the expression of SCFA receptor proteins GPR41 and GPR43 in the colon tissue. Our findings reveal that EcN activates the SCFA/GPRs pathway, thereby preserving intestinal barrier function and alleviating inflammation in a mouse sepsis model. [ABSTRACT FROM AUTHOR]

Context Adrenal crisis (AC) is a life-threatening complication that occurs during follow-up of patients with adrenal insufficiency (AI). No prospective study has thoroughly investigated AC in children with primary and secondary AI. Objective This work aimed to determine the incidence and risk factors for AC in patients with pediatric-onset AI. Methods This multicenter, prospective cohort study conducted in Japan enrolled patients diagnosed with AI at age ≤15 years. The incidence of AC was calculated as events per person-year (PY), and risk factors for AC were assessed using Poisson regression multivariable analysis. Results The study population comprised 349 patients (164 male, 185 female) with a total follow-up of 961 PY. The median age at enrollment was 14.3 years (interquartile range [IQR] 8.5-21.2 years), and the median follow-up was 2.8 years (IQR 2.2-3.3 years). Of these patients, 213 (61%) had primary AI and 136 (39%) had secondary AI. Forty-one AC events occurred in 31 patients during the study period. The calculated incidence of AC was 4.27 per 100 PY (95% CI, 3.15-5.75). Poisson regression analysis identified younger age at enrollment (relative risk [RR] 0.93; 95% CI, 0.89-0.97) and increased number of infections (RR 1.17; 95% CI, 1.07-1.27) as significant risk factors. Female sex (RR 0.99; 95% CI, 0.53-1.86), primary AI (RR 0.65; 95% CI, 0.30-1.41), or equivalent dosage of hydrocortisone per square meter of body area (RR 1.02; 95% CI, 0.96-1.08) was not a significant risk factor. Conclusion A substantial proportion of patients with pediatric-onset AI experience AC. Younger age and an increased number of infections are independent risk factors for developing AC in these patients. [ABSTRACT FROM AUTHOR]

To explore the usefulness of neutrophil-to-lymphocyte count ratio (NLR), procalcitonin (PCT), and interleukin-6 (IL-6) for the severity assessment of bacterial sepsis. This study enrolled 100 patients with bacterial sepsis (disease group) who presented to Jinhua Central Hospital between March 2022 and March 2023 and 90 healthy individuals (control group). The patients were categorized into sepsis (64 cases), severe sepsis (18 cases), and septic shock (18 cases) groups according to the disease severity. The groups were compared in terms of the NLR, PCT, and IL-6, as well as the usefulness of these parameters, both alone and in combination, for the severity assessment of bacterial sepsis. The NLR, PCT, and IL-6 levels were significantly different among the three groups, with increasing values corresponding with disease aggravation. The area under the curve (AUC) values of the combinations of NLR, PCT, and IL-6 levels were higher than those of single markers. The sensitivity and AUC value of the combination of PCT and IL-6 levels were the highest (0.87), with a similar AUC value of the combination of NLR, PCT, and IL-6 (0.865); however, the specificity was significantly improved with the latter (0.938 vs. 0.859). NLR, PCT, and IL-6 levels are significantly increased in bacterial sepsis, and the combination of PCT, and IL-6 levels can improve the sensitivity of the evaluation ability for severe sepsis, and is more economical. [ABSTRACT FROM AUTHOR]

Background: Coagulation abnormalities are common in sepsis patients and are associated with increased mortality. This study aimed to assess the hemostatic profile of sepsis patients using rotational thromboelastometry (ROTEM) and to find the ROTEM parameters best predicting short-term mortality. Methods: We conducted a prospective analysis of consecutive sepsis patients hospitalized in the intensive care unit. The inclusion criteria were diagnosis of sepsis or septic shock and pro-calcitonin concentration >0.5 ng mL−1. Clinical, standard laboratory, and ROTEM analyses were performed. Results: The study group comprised 38 (49%) males and 40 (51%) females. Median Sequential Organ Failure Assessment (SOFA) score was 8 (interquartile range IQR 5–11) points. The most common primary sites of infection were pneumonia (n = 27/35%), intra-abdominal (n = 27/35%), urinary tract infection (n=20/26%), and others (n = 4/6%). The following parameters evaluating fibrinogen function were outside the reference range: clotting time (CT), clot amplitude (A) at 10 and 20 min, and maximal clot firmness (MCF). Out of 78 patients, 28 (36%) died in the intensive care unit. Significant differences between survivors and non-survivors of sepsis were present for the ROTEM parameters assessing fibrinolytic activity. Conclusions: ROTEM in the early phase of sepsis reveals increased coagulation mediated through the function of fibrinogen. Non-survivors showed slightly lower fibrinolytic activity than survivors; however, it was still within test reference values. The highest predicting value was obtained by a model incorporating, among others, extrinsic coagulation pathway fibrinolytic parameters. [ABSTRACT FROM AUTHOR]

Infectious diseases are associated with low iron levels and the induction of hepcidin, the primary protein regulating cellular iron export. Bone morphogenetic protein 6 (BMP6), a key regulator of hepcidin expression, has not yet been analyzed in the plasma of patients with systemic inflammatory response syndrome (SIRS) or sepsis. An analysis of 38 SIRS, 39 sepsis, and 78 septic shock patients revealed similar levels of BMP6 in sepsis and septic shock, which were lower compared to patients with SIRS and healthy controls. Plasma BMP6 levels did not correlate with procalcitonin and C-reactive protein levels in patients with SIRS or sepsis/septic shock. Neither bacterial nor SARS-CoV-2 infections affected plasma BMP6 levels. There was no difference in BMP6 levels between ventilated and non-ventilated patients, or between patients with and without dialysis. Vasopressor therapy did not alter BMP6 levels. Survivors had plasma BMP6 levels similar to non-survivors. Due to the high variability of plasma BMP6 levels, these analyses have limited clinical relevance. Iron, ferritin, and transferrin levels were known in at least 50% of patients but did not correlate with plasma BMP6 levels. In conclusion, this study showed normal BMP6 plasma levels in SIRS, which are reduced in patients with sepsis and septic shock. This suggests that the commonly observed increase in hepcidin levels and the decline in iron levels in SIRS, sepsis, and septic shock are not due to higher BMP6. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs), including cystitis and pyelonephritis, are common. Each year, they account for more than 10 million outpatient visits and more than 3 million emergency department visits. Recurrent UTIs (defined as three in 1 year or two in 6 months) also are common, occurring in 20% to 30% of women. The annual incidence of UTIs is 12.1% among women and 3% among men. Cystitis symptoms include lower abdominal pain, dysuria, and urinary urgency or frequency. Escherichia coli is the most common pathogen. Cystitis often is diagnosed inappropriately when patients have asymptomatic bacteriuria (ie, positive urine culture result without symptoms). This can result in unnecessary antibiotic therapy. For uncomplicated acute cystitis in women, guidelines recommend nitrofurantoin for 5 days, trimethoprim-sulfamethoxazole for 3 days (if local drug-resistance rates are less than 20%), fosfomycin in a single dose, or pivmecillinam for 5 days. Effective prophylactic options for UTI include antibiotics and vaginal estrogen for postmenopausal women. Antibiotics are most effective but are associated with a risk of increased drug resistance. Patients with pyelonephritis present with costovertebral tenderness, fever, and urinary symptoms. Third-generation cephalosporins are preferred for management. Significant complications of pyelonephritis include sepsis or septic shock, obstructive pyelonephritis, emphysematous pyelonephritis, perinephric abscess, and kidney transplant rejection. For pregnant patients with pyelonephritis, hospitalization and intravenous antibiotics are indicated. [ABSTRACT FROM AUTHOR]

Background: As elderly individuals often exhibit heightened vulnerability to infections due to factors such as compromised immune systems, chronic illnesses, and age-related physiological changes, understanding the characteristics and risk factors associated with infectious diseases in this population is crucial. The aim of the present study was to evaluate the characteristics of elderly patients with infectious disease in ED admission and to identify risk factors that influence in-hospital mortality. Material and Method: In this study, we enrolled 448 adult patients diagnosed with infectious diseases such as pneumonia, urinary tract infection, gastroenteritis, meningitis, and cellulitis. The participants were directly admitted to our Emergency Department (ED) from their homes or their relatives' residences between November 1, 2014, and May 31, 2015. We investigated patient's vital signs, disease signs, source of infection, length of staying at hospital, length of staying at emergency service, mortality related scores, laboratory data, treatment and prognosis. Results and Conclusion: The rate of emergency care admissions with an infectious etiology was found as 17%. Average age of patients was 76±8 with 180 (40%) of them being female and 268 (60%) of them being male. Mortality rate was found as 23%. Cox regression analysis concluded that for 65 years or older patients, risk factors that effected mortality were; septic shock, cardiac disease and presence of malignancy, absence of COPD/Asthma, higher pCO2 and lower HCO3 at the time of admission to the emergency service. Calculating MEDS score and APACHE 2 score at admission to the emergency department and intensive care unit can facilitate early intervention, improving recovery prospects. Further research and clinical strategies may benefit from these identified predictors to improve the management and outcomes of elderly patients with infectious diseases in the ED. [ABSTRACT FROM AUTHOR]

Background and Objectives: Sepsis represents a global health challenge and requires advanced diagnostic and prognostic approaches due to its elevated rate of morbidity and fatality. Our study aimed to assess the value of a novel set of six biomarkers combined with severity scores in predicting 28 day mortality among patients presenting with sepsis in the Emergency Department (ED). Materials and Methods: This single-center, observational, prospective cohort included sixty-seven consecutive patients with septic shock and sepsis enrolled from November 2020 to December 2022, categorized into survival and non-survival groups based on outcomes. The following were assessed: procalcitonin (PCT), soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1), the soluble form of the urokinase plasminogen activator receptor (suPAR), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and azurocidin 1 (AZU1), alongside clinical scores such as the Quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SIRS), the Sequential Organ Failure Assessment (SOFA), the Acute Physiology and Chronic Health Evaluation II (APACHE II), the Simplified Acute Physiology Score II and III (SAPS II/III), the National Early Warning Score (NEWS), Mortality in Emergency Department Sepsis (MEDS), the Charlson Comorbidity Index (CCI), and the Glasgow Coma Scale (GCS). The ability of each biomarker and clinical score and their combinations to predict 28 day mortality were evaluated. Results: The overall mortality was 49.25%. Mechanical ventilation was associated with a higher mortality rate. The levels of IL-6 were significantly higher in the non-survival group and had higher AUC values compared to the other biomarkers. The GCS, SOFA, APACHEII, and SAPS II/III showed superior predictive ability. Combining IL-6 with suPAR, AZU1, and clinical scores SOFA, APACHE II, and SAPS II enhanced prediction accuracy compared with individual biomarkers. Conclusion: In our study, IL-6 and SAPS II/III were the most accurate predictors of 28 day mortality for sepsis patients in the ED. [ABSTRACT FROM AUTHOR]

Background: We evaluated the applicability of automated citation screening in developing clinical practice guidelines. Methods: We prospectively compared the efficiency of citation screening between the conventional (Rayyan) and semi-automated (ASReview software) methods. We searched the literature for five clinical questions (CQs) in the development of the Japanese Clinical Practice Guidelines for the Management of Sepsis and Septic Shock. Objective measurements of the time required to complete citation screening were recorded. Following the first screening round, in the primary analysis, the sensitivity, specificity, positive predictive value, and overall screening time were calculated for both procedures using the semi-automated tool as index and the results of the conventional method as standard reference. In the secondary analysis, the same parameters were compared between the two procedures using the final list of included studies after the second screening session as standard reference. Results: Among the five CQs after the first screening session, the highest and lowest sensitivity, specificity, and positive predictive values were 0.241 and 0.795; 0.991 and 1.000; and 0.482 and 0.929, respectively. In the secondary analysis, the highest sensitivity and specificity in the semi-automated citation screening were 1.000 and 0.997, respectively. The overall screening time per 100 studies was significantly shorter with semi-automated than with conventional citation screening. Conclusion: The potential advantages of the semi-automated method (shorter screening time and higher discriminatory rate for the final list of studies) warrant further validation. [ABSTRACT FROM AUTHOR]

Abstract Background Senescent immune cells exhibit altered gene expression and resistance to apoptosis. The prevalence of these cells increases with age and emerging data implicate senescence-associated maladaptive signaling as a potential contributor to sepsis and septic shock. The senolytic drug fisetin promotes clearance of senescent cells and is hypothesized to mitigate septic responses to infection. Methods We are conducting a multi-center, randomized, double-blinded, adaptive allocation phase 2 clinical trial to assess the efficacy of the senolytic drug fisetin in preventing clinical deterioration of elderly patients diagnosed with sepsis. We intend to enroll and randomize 220 elderly patients (age > 65) with the clinical diagnosis of sepsis to receive either fisetin as a single oral dose of 20 mg/kg, fisetin in two oral doses of 20 mg/kg each spaced 1 day apart, or placebo. The primary outcome will be changed in the composite of cardiovascular, respiratory, and renal sequential organ failure assessment scores at 7 days from enrollment. Secondary outcomes include quantification of senescent CD3 + cells at 7 days, and 28-day assessments of organ failure-free days, days in an intensive care unit, and all-cause mortality. Discussion This multi-center, randomized, double-blinded trial will assess the efficacy of fisetin in preventing clinical deterioration in elderly patients with sepsis and measure the effects of this drug on the prevalence of senescent immune cells. We intend that the results of this phase 2 trial will inform the design of a larger phase 3 study. Trial registration This trial is registered to ClinicalTrials.gov under identifier NCT05758246, first posted on March 7, 2023.

Abstract Objective To assess the predictive abilities of Doppler‐based resistive index and plasma biomarkers of endothelial cell activation in identifying persistent acute kidney injury (pAKI) among patients with septic shock. Method Patients diagnosed with septic shock were categorized into none AKI (n = 25), transient AKI (tAKI, n = 47), and pAKI (n = 48) groups. Kidney function parameters (urine output, serum creatinine, and serum urea) were measured within the initial 24 h upon intensive care unit (ICU) admission. The Doppler‐based resistive index, and the plasma biomarkers [fractalkine, soluble E‐Selectin (sE‐Selectin), and soluble intercellular adhesion molecule‐1 (sICAM‐1)] were evaluated upon admission to the ICU. Results The predictive capacity of Doppler‐based resistive index for distinguishing pAKI at day 3 from none AKI/tAKI in septic shock patients was moderate, with sensitivity of 47.92% and specificity of 76.39%. Fractalkine levels displayed significant differences across groups and exhibited a favorable predictive ability for pAKI at day 3 (AUC = 0.800), while sE‐Selectin and sICAM‐1 showed moderate predictive abilities (AUC = 0.636 and 0.634, respectively). Comparative analysis of predictive models demonstrated that incorporating kidney function parameters, Doppler‐based resistive index, and plasma biomarkers yielded the highest AUC of 0.903, followed closely by the model utilizing serum creatinine, urine output, and plasma fractalkine, with an AUC of 0.896. Conclusion Integrating kidney function parameters, along with Doppler‐based resistive index and plasma biomarkers of endothelial cell activation, yielded the strongest predictive model for pAKI. Additionally, the combination of serum creatinine, urine output, and plasma fractalkine shows promise in risk assessment and management strategies for pAKI.

Abstract Background Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. Methods This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. Results A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P 85 beats per minute (bpm). The log-rank test revealed in terms of the 28-day mortality, the hazard ratio (HR) (95% confidence interval [CI]) was 1.92 (1.78—2.06, P 85 bpm. Conclusion Patients with septic shock whose heart rate was controlled no more than 85 bpm during ICU stay received survival benefit in terms of 28-day, ICU and in-hospital mortality.

Anaerobic infection is one of the severe wound infections caused by anaerobic microorganisms. According to statistical data, patients with complications of anaerobic infection have a high mortality rate, so early diagnosis and appropriate therapy are a key to the effective treatment of this pathology. To date, very few clinical cases with a combined effective treatment for anaerobic wound infection have been described. This article considers the step-by-step diagnosis and treatment for anaerobic infection in a serviceman who was injured as a result of military operations.