Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth.

BACKGROUND: The use of azithromycin reduces maternal infection in women during unplanned cesarean delivery, but its effect on those with planned vaginal delivery is unknown. Data are needed on whether an intrapartum oral dose of azithromycin would reduce maternal and offspring sepsis or death. METHODS: In this multicountry, placebo-controlled, randomized trial, we assigned women who were in labor at 28 weeks' gestation or more and who were planning a vaginal delivery to receive a single 2-g oral dose of azithromycin or placebo. The two primary outcomes were a composite of maternal sepsis or death and a composite of stillbirth or neonatal death or sepsis. During an interim analysis, the data and safety monitoring committee recommended stopping the trial for maternal benefit. RESULTS: A total of 29,278 women underwent randomization. The incidence of maternal sepsis or death was lower in the azithromycin group than in the placebo group (1.6% vs. 2.4%), with a relative risk of 0.67 (95% confidence interval [CI], 0.56 to 0.79; P<0.001), but the incidence of stillbirth or neonatal death or sepsis was similar (10.5% vs. 10.3%), with a relative risk of 1.02 (95% CI, 0.95 to 1.09; P = 0.56). The difference in the maternal primary outcome appeared to be driven mainly by the incidence of sepsis (1.5% in the azithromycin group and 2.3% in the placebo group), with a relative risk of 0.65 (95% CI, 0.55 to 0.77); the incidence of death from any cause was 0.1% in the two groups (relative risk, 1.23; 95% CI, 0.51 to 2.97). Neonatal sepsis occurred in 9.8% and 9.6% of the infants, respectively (relative risk, 1.03; 95% CI, 0.96 to 1.10). The incidence of stillbirth was 0.4% in the two groups (relative risk, 1.06; 95% CI, 0.74 to 1.53); neonatal death within 4 weeks after birth occurred in 1.5% in both groups (relative risk, 1.03; 95% CI, 0.86 to 1.24). Azithromycin was not associated with a higher incidence in adverse events. CONCLUSIONS: Among women planning a vaginal delivery, a single oral dose of azithromycin resulted in a significantly lower risk of maternal sepsis or death than placebo but had little effect on newborn sepsis or death. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; A-PLUS ClinicalTrials.gov number, NCT03871491.).

Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial.

BACKGROUND: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications. METHODS: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125. FINDINGS: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22). INTERPRETATION: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea. FUNDING: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong.

High incidence of immune-mediated inflammatory diseases in sepsis survivors: A nationwide exposed-nonexposed epidemiological study.

OBJECTIVE: Sepsis is characterized by an excessive release of inflammatory cytokines. Cytokine dysregulation is pivotal to the pathophysiology of immune-mediated inflammatory diseases (IMIDs). We aimed to analyze the incidence of IMIDs in patients who survived sepsis. METHODS: We performed a matched-cohort study using the National Medico-Administrative Hospital database in order to analyze the association between sepsis and incident IMIDs in 2020 in France. Sepsis was defined by the combination of at least one infection diagnosis code and one organ failure code. Patients with a first sepsis diagnosed in 2020 were randomly matched with patients admitted during the same period for acute myocardial infarction (AMI) with an exact matching procedure using age, gender, and comorbidities as matching variables. The main outcome was an IMID diagnosis in a 9-month follow-up period starting the first day of hospitalization for sepsis or AMI. RESULTS: In France, the incidence rate of IMIDs after a sepsis in 2020-analyzed in 62,257 patients-was of 7956 (95% confidence interval [95% CI] 7392-8520) per 100,000 patient-years. As compared to the AMI population, we observed an increased risk for IMIDs of 2.80 (hazard ratio [HR]; 95% CI [2.22-3.54]) starting from day 16 after admission in the sepsis population. The risk of IMIDs onset in sepsis survivors depended on the type of IMIDs and was higher for immune thrombocytopenia (5.51 [1.97-15.4]), autoimmune hemolytic anemia (HR 4.83 [1.45-16.1]), and antineutrophil cytoplasmic antibody-associated vasculitis (4.66 [2.05-10.6]). Association between sepsis and IMIDs onset appeared well balanced across pathogen categories. CONCLUSION: Our study shows a high incidence of IMIDs among sepsis survivors.

In-Hospital Neurologic Complications, Neuromonitoring, and Long-Term Neurologic Outcomes in Patients With Sepsis: A Systematic Review and Meta-Analysis.

OBJECTIVES: Although delirium is well described in patients with sepsis, there are limited data on other neurologic complications. We aimed to systematically review the prevalence, neuromonitoring tools, and neurocognitive outcomes in sepsis patients with neurologic complications. DATA SOURCES: MEDLINE and six other databases (Embase, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov ) were searched through January 2023. STUDY SELECTION: Studies of adult patients with sepsis reported neurologic complications, use of neuromonitoring tools, neuropathology, and cognitive outcomes. DATA EXTRACTION: Two independent reviewers extracted the data. Random-effect meta-analyses were used to pool data. DATA SYNTHESIS: Seventy-four studies ( n = 146,855) were included. Neurologic complications were reported in 38 studies ( n = 142,193) including septic encephalopathy (36%, 95% CI, 27-46%; I 2 = 99%), ischemic stroke (5%, 95% CI, 2.1-11.5; I 2 = 99%), intracranial hemorrhage (2%, 95% CI, 1.0-4.4%; I 2 = 96%), seizures (1%, 95% CI, 0.2-7%; I 2 = 96%), posterior reversible encephalopathy syndrome (9%), and hypoxic-ischemic brain injury (7%). In the meta-regression analysis, pulmonary infection, sepsis induced by a gram-positive organism, higher sequential organ failure assessment score, acute physiology and chronic health evaluation II score at admission, and longer ICU length of stay were associated with higher risk of developing septic encephalopathy. Three studies ( n = 159) reported postmortem neuropathological findings, acute brain injury was noted in 47% of patients. Twenty-six studies ( n = 1,358) reported the use of neuromonitoring tools, electroencephalogram was the most used tool for seizure detection. Transcranial Doppler and near infrared spectroscopy were used for monitoring cerebral hemodynamic changes to detect early ischemia. Six studies reported cognitive outcomes ( n = 415) up to 12 months postdischarge and cognitive impairment (≥ one domain) was reported in 30%. CONCLUSIONS: In-hospital neurologic complications are common in patients with sepsis. However, the mechanism and timing of those sepsis-associated complications are poorly understood and there are limited data on standardized neuromonitoring in this population.

Quantifying the Impact of Alternative Definitions of Sepsis-Associated Acute Kidney Injury on its Incidence and Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVES: To derive a pooled estimate of the incidence and outcomes of sepsis-associated acute kidney injury (SA-AKI) in ICU patients and to explore the impact of differing definitions of SA-AKI on these estimates. DATA SOURCES: Medline, Medline Epub, EMBASE, and Cochrane CENTRAL between 1990 and 2023. STUDY SELECTION: Randomized clinical trials and prospective cohort studies of adults admitted to the ICU with either sepsis and/or SA-AKI. DATA EXTRACTION: Data were extracted in duplicate. Risk of bias was assessed using adapted standard tools. Data were pooled using a random-effects model. Heterogeneity was assessed by using a single covariate logistic regression model. The primary outcome was the proportion of participants in ICU with sepsis who developed AKI. DATA SYNTHESIS: A total of 189 studies met inclusion criteria. One hundred fifty-four reported an incidence of SA-AKI, including 150,978 participants. The pooled proportion of patients who developed SA-AKI across all definitions was 0.40 (95% CI, 0.37-0.42) and 0.52 (95% CI, 0.48-0.56) when only the Risk Injury Failure Loss End-Stage, Acute Kidney Injury Network, and Improving Global Outcomes definitions were used to define SA-AKI. There was significant variation in the incidence of SA-AKI depending on the definition of AKI used and whether AKI defined by urine output criteria was included; the incidence was lowest when receipt of renal replacement therapy was used to define AKI (0.26; 95% CI, 0.24-0.28), and highest when the Acute Kidney Injury Network score was used (0.57; 95% CI, 0.45-0.69; p < 0.01). Sixty-seven studies including 29,455 participants reported at least one SA-AKI outcome. At final follow-up, the proportion of patients with SA-AKI who had died was 0.48 (95% CI, 0.43-0.53), and the proportion of surviving patients who remained on dialysis was 0.10 (95% CI, 0.04-0.17). CONCLUSIONS: SA-AKI is common in ICU patients with sepsis and carries a high risk of death and persisting kidney impairment. The incidence and outcomes of SA-AKI vary significantly depending on the definition of AKI used.

Validation of Adult Sepsis Event and Epidemiologic Analysis of Sepsis Prevalence and Mortality Using Adult Sepsis Event's Electronic Health Records-Based Sequential Organ Failure Assessment Criteria: A Single-Center Study in South Korea.

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.

The Impact of Common Variations in Sequential Organ Failure Assessment Score Calculation on Sepsis Measurement Using Sepsis-3 Criteria: A Retrospective Analysis Using Electronic Health Record Data.

OBJECTIVES: To assess the impact of different methods of calculating Sequential Organ Failure Assessment (SOFA) scores using electronic health record data on the incidence, outcomes, agreement, and predictive validity of Sepsis-3 criteria. DESIGN: Retrospective observational study. SETTING: Five Massachusetts hospitals. PATIENTS: Hospitalized adults, 2015 to 2022. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We defined sepsis as a suspected infection (culture obtained and antibiotic administered) with a concurrent increase in SOFA score by greater than or equal to 2 points (Sepsis-3 criteria). Our reference SOFA implementation strategy imputed normal values for missing data, used Pa o2 /F io2 ratios for respiratory scores, and assumed normal baseline SOFA scores for community-onset sepsis. We then implemented SOFA scores using different missing data imputation strategies (averaging worst values from preceding and following days vs. carrying forward nonmissing values), imputing respiratory scores using Sp o2 /F io2 ratios, and incorporating comorbidities and prehospital laboratory data into baseline SOFA scores. Among 1,064,459 hospitalizations, 297,512 (27.9%) had suspected infection and 141,052 (13.3%) had sepsis with an in-hospital mortality rate of 10.3% using the reference SOFA method. The percentage of patients missing SOFA components for at least 1 day in the infection window was highest for Pa o2 /F io2 ratios (98.6%), followed by Sp o2 /F io2 ratios (73.5%), bilirubin (68.5%), and Glasgow Coma Scale scores (57.2%). Different missing data imputation strategies yielded near-perfect agreement in identifying sepsis (kappa 0.99). However, using Sp o2 /F io2 imputations yielded higher sepsis incidence (18.3%), lower mortality (8.1%), and slightly lower predictive validity for mortality (area under the receiver operating curves [AUROC] 0.76 vs. 0.78). For community-onset sepsis, incorporating comorbidities and historical laboratory data into baseline SOFA score estimates yielded lower sepsis incidence (6.9% vs. 11.6%), higher mortality (13.4% vs. 9.6%), and higher predictive validity (AUROC 0.79 vs. 0.75) relative to the reference SOFA implementation. CONCLUSIONS: Common variations in calculating respiratory and baseline SOFA scores, but not in handling missing data, lead to substantial differences in observed incidence, mortality, agreement, and predictive validity of Sepsis-3 criteria.

Intersection of sepsis, atrial fibrillation, and severe obesity: a population-based analysis in the United States.

BACKGROUND: Atrial fibrillation (AF) is an indicator of poor prognosis in patients with sepsis and can increase the risk of stroke and mortality. Data on the impact of severe obesity on the outcomes of sepsis complicated by AF remains poorly understood. METHODS: National Inpatient Sample (2018) and ICD-10 CM codes were used to identify the principal sepsis admissions with AF. We assessed comorbidities and outcomes of sepsis in people without obesity (BMI < 30) vs. non-severe obesity (BMI 30-35) and severe obesity (BMI > 35) cohorts. We also did a subgroup analysis to further stratify obesity based on metabolic health and analyzed the findings. The primary outcomes were the prevalence and adjusted odds of AF, AF-associated stroke, and all-cause mortality in sepsis by obesity status. Multivariable regression analyses were adjusted for patient- and hospital-level characteristics and comorbidities. RESULTS: Our main analysis showed that of the 1,345,595 sepsis admissions, the severe obesity cohort was the youngest (median age 59 vs. non-severe 64 and people without obesity 68 years). Patients with obesity, who were often female, were more likely to have hypertension, diabetes, congestive heart failure, chronic pulmonary disease, and chronic kidney disease. The crude prevalence of AF was highest in non-severe obesity (19.9%). The adjusted odds of AF in non-severe obesity (OR 1.21; 95% CI:1.16-1.27) and severe obesity patients with sepsis (OR 1.49; 95% CI:1.43-1.55) were significantly higher than in people without obesity (p < 0.001). Paradoxically, the rates of AF-associated stroke (1%, 1.5%, and 1.7%) and in-hospital mortality (3.3%, 4.9%, and 7.1%) were lowest in the severe obesity cohort vs. the non-severe and people without obesity cohorts, respectively. On multivariable regression analyses, the all-cause mortality revealed lower odds in sepsis-AF patients with severe obesity (OR 0.78; 95% CI:0.67-0.91) or non-severe obesity (OR 0.63; 95% CI:0.54-0.74) vs. people without obesity. There was no significant difference in stroke risk. CONCLUSIONS: A higher prevalence of cardiovascular comorbidities can be linked to a higher risk of AF in people with obesity and sepsis. Paradoxically, lower rates of stroke and all-cause mortality secondary to AF in people with obesity and sepsis warrant further investigation.

Complications Following Transrectal and Transperineal Prostate Biopsy: Results of the ProBE-PC Randomized Clinical Trial.

PURPOSE: Transrectal prostate biopsy has come under scrutiny due to potential for postbiopsy infections and transperineal prostate biopsy is being offered as the safer alternative. However, there is a lack of randomized comparative studies. Our goal was to directly evaluate infectious and noninfectious complications following the 2 biopsy procedures. MATERIALS AND METHODS: We conducted a prospective, pragmatic, randomized clinical study in men undergoing prostate biopsy. The participants underwent either transrectal or transperineal prostate biopsy in the office under local anesthesia. The primary outcome was a 30-day composite infectious complication rate, comprising of 1 or more components including fever, genitourinary infection, antibiotic prescriptions, office or emergency visits, hospitalization, or sepsis. Secondary outcomes included 30-day composite noninfectious complications (urinary or hemorrhagic). RESULTS: Of the 763 randomized participants, 718 underwent either transrectal (351) or transperineal (367) prostate biopsy. A composite infectious complication event occurred in 9 participants (2.6%) in the transrectal and 10 participants (2.7%) in the transperineal group (odds ratio, 1.06; 95% CI, 0.43 to 2.65; P = .99). None of the participants developed sepsis in either group. There were no between-group differences in any of the individual component infectious events. A composite noninfectious complication occurred in 6 (1.7%) and 8 (2.2%) participants in the transrectal and transperineal groups, respectively (odds ratio, 1.28; 95% CI, 0.44 to 3.73; P = .79). No participants required hospitalization or other interventions. CONCLUSIONS: Among men undergoing transperineal or transrectal prostate biopsy, we could not demonstrate any difference in the infectious or noninfectious complications. Both biopsy approaches remain clinically viable and safe.

Apnea, Intermittent Hypoxemia, and Bradycardia Events Predict Late-Onset Sepsis in Infants Born Extremely Preterm.

OBJECTIVE: The objective of this study was to examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks of gestational age) on vs off invasive mechanical ventilation. STUDY DESIGN: This is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in 5 level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean gestational age: 26.4 weeks, SD 1.71). Monitoring data were available and analyzed for 719 infants (47 512 patient-days); of whom, 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72 hours after birth and ≥5-day antibiotics). RESULTS: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer events with oxygen saturation <80% (IH80) and more bradycardia events before sepsis. IH events were associated with higher sepsis risk but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model including postmenstrual age, cardiorespiratory variables (apnea, periodic breathing, IH80, and bradycardia), and ventilator status predicted sepsis with an area under the receiver operator characteristic curve of 0.783. CONCLUSION: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis.

Fever in focus: Symptoms, diagnoses and treatment of febrile children in Ghana-A longitudinal hospital study.

BACKGROUND: Healthcare resources are often limited in areas of sub-Saharan Africa. This makes accurate and timely diagnoses challenging and delays treatment of childhood febrile illness. We explored longitudinal characteristics related to symptoms, diagnosis and treatment of hospitalised febrile children in a rural area of Ghana highly endemic for malaria. METHODS: Febrile children under 15 years, admitted to the study hospital paediatric ward, were recruited to the study and clinical data were collected throughout hospitalisation. Descriptive statistics were reported for all cases; for longitudinal analyses, a subset of visits with limited missing data was used. RESULTS: There were 801 hospitalised children included in longitudinal analyses. Malaria (n = 581, 73%) and sepsis (n = 373, 47%) were the most prevalent suspected diagnoses on admission. One-third of malaria suspected diagnoses (n = 192, 33%) were changed on the discharge diagnosis, compared to 84% (n = 315) of sepsis suspected diagnoses. Among malaria-only discharge diagnoses, 98% (n/N = 202/207) received an antimalarial and 33% (n/N = 69/207) an antibiotic; among discharge diagnoses without malaria, 28% (n/N = 108/389) received an antimalarial and 83% (n/N = 324/389) an antibiotic. CONCLUSIONS: Suspected diagnoses were largely based on clinical presentation and were frequently changed; changed diagnoses were associated with lingering symptoms, underscoring the need for faster and more accurate diagnostics. Medications were over-prescribed regardless of diagnosis stability, possibly because of a lack of confidence in suspected diagnoses. Thus, better diagnostic tools are needed for childhood febrile illnesses to enhance the accuracy of and confidence in diagnoses, and to cut down unjustified medication use, reducing the risk of antimicrobial and malaria resistance.

Antisecretory factor in breastmilk is associated with reduced incidence of sepsis in preterm infants.

BACKGROUND: Antisecretory Factor (AF) is a protein present in breastmilk that regulates inflammatory processes. We aimed to investigate the level of AF in mothers' own milk (MOM) in relation to sepsis and other neonatal morbidities in preterm infants. METHODS: Samples of breastmilk and infant plasma were collected at 1, 4, and 12 weeks after birth from 38 mothers and their 49 infants born before 30 weeks gestation. AF-compleasome in MOM was determined by a sandwich enzyme-linked immunosorbent assay (ELISA) and inflammatory markers in infant plasma by a panel of 92 inflammatory proteins. Neonatal treatments and outcomes were recorded. RESULTS: The level of AF in MOM week 1 was lower for infants with later sepsis compared to no sepsis (p = 0.005). Corrected for nutritional intake of MOM, higher levels of AF decreased the risk for sepsis, OR 0.24. AF in MOM week 1 was negatively correlated to inflammatory proteins in infant plasma week 4, markedly IL-8, which was also associated with infant sepsis. Overall, higher AF levels in MOM was associated with fewer major morbidities of prematurity. CONCLUSION: Mother's milk containing high levels of antisecretory factor is associated with reduced risk for sepsis and inflammation in preterm infants. IMPACT: High level of antisecretory factor (AF) in mothers' own milk is associated with less risk for later sepsis in preterm infants. Receiving mothers' milk with low AF levels during the first week after birth is correlated with more inflammatory proteins in infant's plasma 2-4 weeks later. Human breastmilk has anti-inflammatory properties, and antisecretory factor in mothers' own milk is a component of potential importance for infants born preterm. The findings suggest that food supplementation with AF to mothers of preterm infants to increase AF-levels in breastmilk may be a means to decrease the risk of inflammatory morbidities of prematurity.

Markers of platelet activation foR identification of late onset sEpsis in infaNTs: PARENT study protocol.

BACKGROUND: Newborns are at high risk of sepsis. At present there is no definitive "rule in" blood test for sepsis at the point of clinical concern. A positive blood culture remains the gold standard test for neonatal sepsis, however laboratory markers that correlate prospectively with culture positive sepsis could aid clinicians in making decisions regarding administration of empiric antibiotic therapies. METHODS: This multi-site, prospective observational study will take place in two neonatal intensive care units (National Maternity Hospital and Rotunda Hospital, Dublin). Neonates born at less than 34 weeks will be enroled and informed consent obtained prior to late onset sepsis work up. If at any point subsequently during their neonatal intensive care stay they develop signs and symptoms of possible sepsis requiring blood culture, an additional sodium citrate sample will be obtained. Infants will be categorised into three groups as follows: (i) culture positive sepsis, (ii) culture negative sepsis where an infant receives 5 days of antibiotics (iii) non sepsis. Our primary outcome is to establish if differential platelet/endothelial activation can prospectively identify neonatal culture positive late onset sepsis. TRIAL REGISTRATION NUMBER: NCT05530330 IMPACT: Preterm infants are a high risk group for the development of sepsis which is a major cause of mortality in this population. Platelets have been associated with host response to invasive bacterial infections both in animal models and translational work. A positive blood culture is the gold standard test for neonatal sepsis but can be unreliable due to limited blood sampling in the very low birth weight population. This study hopes to establish if platelet/endothelial associated plasma proteins can prospectively identify late onset neonatal sepsis.

The effect of hospital caseload on perioperative mortality, morbidity and costs in bladder cancer patients undergoing radical cystectomy: results of the German nationwide inpatient data.

OBJECTIVES: To determine a data-based optimal annual radical cystectomy (RC) hospital volume threshold and evaluate its clinical significance regarding perioperative mortality, complications, length of hospital stay, and hospital revenues. MATERIAL AND METHODS: We used the German Nationwide inpatient Data, provided by the Research Data Center of the Federal Bureau of Statistics (2005-2020). 95,841 patients undergoing RC were included. Based on ROC analyses, the optimal RC threshold to reduce mortality, ileus, sepsis, transfusion, hospital stay, and costs is 54, 50, 44, 44, 71 and 76 cases/year, respectively. Therefore, we defined an optimal annual hospital threshold of 50 RCs/year, and we also used the threshold of 20 RCs/year proposed by the EAU guidelines to perform multiple patient-level analyses. RESULTS: 28,291 (29.5%) patients were operated in low- (< 20 RC/year), 49,616 (51.8%) in intermediate- (20-49 RC/year), and 17,934 (18.7%) in high-volume (≥ 50 RC/year) centers. After adjusting for major risk factors, high-volume centers were associated with lower inpatient mortality (OR 0.72, 95% CI 0.64-0.8, p < 0.001), shorter length of hospital stay (2.7 days, 95% CI 2.4-2.9, p < 0.001) and lower costs (457 Euros, 95% CI 207-707, p < 0.001) compared to low-volume centers. Patients operated in low-volume centers developed more perioperative complications such as transfusion, sepsis, and ileus. CONCLUSIONS: Centralization of RC not only improves inpatient morbidity and mortality but also reduces hospital stay and costs. We propose a threshold of 50 RCs/year for optimal outcomes.

Construction and validation of the nomogram predictive model for post-percutaneous nephrolithotomy urinary sepsis.

OBJECTIVE: This study aimed to construct and validate a simple and accurate clinical nomogram for predicting the occurrence of post-percutaneous nephrolithotomy sepsis, aiming to assist urologists in the early identification, warning, and early intervention of urosepsis, and to provide certain evidence-based medicine basis. METHODS: This study included patients who underwent PCNL surgery due to kidney or upper ureteral stones at the Department of Urology, Affiliated Hospital of Zunyi Medical University, from January 2019 to September 2022. This study utilized univariate and multivariate logistic regression analysis to screen and evaluate the risk factors for sepsis and construct a predictive model. An evaluation was performed using the receiver operating characteristic curve, calibration curve, and decision curve analysis curve. All statistical analyses were conducted using R version 4.2. RESULTS: A total of 946 patients who underwent post-PCNL were included in this study, among whom 69 patients (7.29%) developed post-PCNL urinary sepsis. Multiple-factor logistic regression analysis identified four independent risk factors associated with post-PCNL urinary sepsis, including positive urinary nitrite (OR = 5.9, P < 0.001), positive urine culture (OR = 7.54, P < 0.001), operative time ≥ 120 min (OR = 20.93, P = 0.0052), and stone size ≥ 30 mm (OR = 13.81, P = 0.0015). The nomogram model demonstrated good accuracy with an AUC value of 0.909, and in the validation cohort, the AUC value was 0.922. The calibration curve indicated a better consistency between the predictive line chart and the actual occurrence of post-PCNL urinary sepsis. The decision curve analysis curve showed favorable clinical utility. CONCLUSION: Preoperative positive urine culture, positive urinary nitrite, operative time ≥ 120 min, and stone size ≥ 30 mm are independent risk factors for developing post-PCNL urinary sepsis. The constructed line chart based on these factors effectively assesses the risk of urinary sepsis in patients after PCNL.

Urosepsis 30-day mortality, morbidity, and their risk factors: SERPENS study, a prospective, observational multi-center study.

PURPOSE: To provide a descriptive report of mortality and morbidity in the first 30 days of diagnosis of urosepsis. Secondary aim is to identify risk factors of unfavourable outcomes. METHODS: Prospective observational multicentre cohort study conducted from September 2014 to November 2018 in European hospitals. Adult patients (≥ 18 years) diagnosed with acute urosepsis according to Sepsis-2 criteria with confirmed microbiological infection were included. Outcomes were classified in one of four health states: death, multiple organ failure, single organ failure, and recovery at day 30 from onset of urosepsis. Descriptive statistics and ordinal logistic regression analysis was performed. RESULTS: Three hundred and fifty four patients were recruited, and 30-day mortality rate was 2.8%, rising to 4.6% for severe sepsis. All patients who died had a SOFA score of ≥ 2 at diagnosis. Upon initial diagnosis, 79% (n = 281) of patients presented with OF. Within 30 days, an additional 5% developed OF, resulting in a total of 84% affected. Charlson score (OR 1.14 CI 1.01-1.28), patients with respiratory failure at baseline (OR 2.35, CI 1.32-4.21), ICU admission within the past 12 months (OR 2.05, CI 1.00-4.19), obstruction causative of urosepsis (OR 1.76, CI 1.02-3.05), urosepsis with multi-drug-resistant(MDR) pathogens (OR 2.01, CI 1.15-3.53), and SOFA baseline score ≥ 2 (OR 2.74, CI 1.49-5.07) are significantly associated with day 30 outcomes (OF and death). CONCLUSIONS: Impact of comorbidities and MDR pathogens on outcomes highlights the existence of a distinct group of patients who are prone to mortality and morbidity. These findings underscore the need for the development of pragmatic classifications to better assess the severity of UTIs and guide management strategies. STUDY REGISTRATION: Clinicaltrials.gov registration number NCT02380170.

Risk factors of early infectious complications after ureterorenoscopy for stone disease: a prospective study.

PURPOSE: To prospectively evaluate the rate and associated risk factors of early infectious complications after ureterorenoscopy for urolithiasis. METHODS: After ethical committee approval, 400 therapeutic retrograde ureterorenoscopy procedures between August 3, 2020 and November 24, 2021 were included for analysis in a single-center study. Postoperative infection was defined as an afebrile urinary tract infection, fever (≥ 38 °C) with pyuria (≥ 300 WBC/µL) or proven urinary pathogen, and urosepsis. The primary outcome was the rate of infectious complications after ureterorenoscopy. Secondary outcomes were the perioperative factors that increased the risk of infectious complications within 30 days of surgery using univariate and multivariate logistic regression analysis. RESULTS: Twenty-nine of four hundred (7.3%) patients developed an infectious complication within 30 days after ureterorenoscopy. Ten (2.5%) patients developed an afebrile urinary tract infection, eight (2.0%) developed fever with pyuria, five (1.3%) febrile urinary tract infection, and six (1.5%) urosepsis. On univariate analysis, preoperative stent-type JFil® pigtail suture stent was significantly associated with the dependent variable (p < 0.001). On multivariate logistic regression analysis, older age (OR 1.035; 95% CI 1.006-1.070; p = 0.02) was found to be significantly associated with developing a postoperative infectious complication. CONCLUSIONS: A 7.3% rate of postoperative infectious complications and 1.5% urosepsis rate were observed after therapeutic ureterorenoscopy, without the need of intensive care admission. The only significant risk factors were preoperative stent type (JFil® pigtail suture stent) on univariate analysis, and older age on multivariate logistic regression analysis. Further multicentric prospective observational data are needed in this field.

Sepsis and Septic Shock in Patients Undergoing Thyroidectomy: Incidence, Risk Factors, and Outcomes.

INTRODUCTION: Postoperative sepsis represents a rare complication following thyroidectomy. We aimed to explore the incidence, risk factors, sources, and outcomes of postoperative sepsis and septic shock among adult patients undergoing thyroidectomy. METHODS: Data from the American College of Surgeons National Surgical Quality Improvement Program were used in this retrospective cohort study. Patients aged ≥18 y who underwent elective thyroidectomy between 2005 and 2019 were included. Multivariable binary logistic regression models were computed to explore risk factors and outcomes of 30-d sepsis and septic shock. RESULTS: Among the 180,373 included patients, 0.1% developed sepsis or septic shock. Male gender, low body mass index, American Society of Anesthesiologists classes 3-5, functional dependence, smoking, diabetes mellitus, pulmonary disease, inpatient surgery, malignant indication, clean-contaminated wound classification, and operation time ≥150 min were significant risk factors for development of sepsis or septic shock. Common infectious sources of sepsis included surgical site infections (29.6%), pneumonia (18.6%), urinary tract infections (16.2%), and multiple infections (6.9%). Patients with postoperative sepsis or septic shock were significantly more likely to develop complications, including wound disruption, stroke, cardiac and renal complications, thromboembolism, prolonged length of stay, unplanned reoperation, and mortality. CONCLUSIONS: Sepsis is rare following thyroidectomy. Our study provides insight into risk factors and procedural characteristics which may contribute to the development of postoperative sepsis or septic shock in this population.

Population-based genomic surveillance of Pseudomonas aeruginosa causing bloodstream infections in a large Canadian health region.

PURPOSE: Population-based surveillance was undertaken to determine clinical factors, susceptibility patterns, and incidence rates (IR) of Pseudomonas aeruginosa causing bloodstream infections (BSIs) in a Canadian region (2010-2018). METHODS: We combined clinical data with genomics to characterize P. aeruginosa (BSIs) (n = 167) in a well-defined Canadian (Calgary) human population over a 9-year period (2010-2018). RESULTS: The annual population IR per 100,000 patient years increased from 3.4/100,000 in 2010 to 5.9/100,000 in 2018, with the highest IRs in elderly males from the hospital setting. Over a quarter of patients presented with febrile neutropenia, followed by urinary tract infections and pneumonia. Antimicrobial resistance (AMR) rates and determinants were rare. The P. aeruginosa population was polyclonal consisting of three dominant sequence types (STs), namely ST244, ST111, and ST17. Antimicrobial-susceptible ST244 was the most common clone and belonged to three clades (A, B, C). The ST244 IR/100,000 increased over time due to the expansion of clade C. Multidrug-resistant ST111 was the second most common clone and IR/100,000 decreased over time. ST111 belonged to three clades (A, B, C) with clade C containing blaVIM-2. Different serotypes were linked to various STs. The IR/100,000 of P. aeruginosa that belonged to serotypes O6 increased significantly over time. CONCLUSION: An effective multivalent vaccine consisting of five serotypes (O1, O3, O5, O6, O11) would confer protection to > 70% of Calgary residents with P. aeruginosa BSIs. This study has provided a unique perspective of the population dynamics over time of P. aeruginosa STs, clades, and serotypes responsible for BSIs.

Understanding the biases to sepsis surveillance and quality assurance caused by inaccurate coding in administrative health data.

PURPOSE: Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care. METHODS: We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015-2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information. RESULTS: ICD-coding of sepsis in IAHD showed high positive predictive value (76.9-85.7% depending on sepsis definition), but low sensitivity (26.8-38%), which led to an underestimation of sepsis incidence (1.4% vs. 3.3% for severe sepsis-1). Not naming sepsis in the chart was strongly associated with under-coding of sepsis. The frequency of correctly naming sepsis and ICD-coding of sepsis varied strongly between hospitals (range of sensitivity of naming: 29-71.7%, of ICD-diagnosis: 10.7-58.5%). Risk-adjusted mortality of sepsis per hospital calculated from coding in IAHD showed no substantial correlation to reference standard risk-adjusted mortality (r = 0.09). CONCLUSION: Due to the under-coding of sepsis in IAHD, previous epidemiological studies underestimated the burden of sepsis in Germany. There is a large variability between hospitals in accuracy of diagnosing and coding of sepsis. Therefore, IAHD alone is not suited to assess quality of sepsis care.