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Science Advances, Volume 9, Issue 21, May 2023.

Abstract Background Little evidence exists regarding the prevalence of pathogens in bloodstream infections (BSIs), the mortality risk, and the benefit of combination therapy over monotherapy. This study aims to describe patterns of empiric antimicrobial therapy, and the epidemiology of Gram-negative pathogens, and to investigate the effect of appropriate therapy and appropriate combination therapy on the mortality of patients with BSIs. Methods This was a retrospective cohort study including all patients with BSIs of Gram-negative pathogens from January 2017 to December 2022 in a Chinese general hospital. The in-hospital mortality was compared between appropriate and inappropriate therapy, and between monotherapy and combination therapy for patients receiving appropriate therapy. We used Cox regression analysis to identify factors independently associated with in-hospital mortality. Results We included 205 patients in the study, of whom 147 (71.71%) patients received appropriate therapy compared with 58 (28.29%) who received inappropriate therapy. The most common Gram-negative pathogen was Escherichia coli (37.56%). 131 (63.90%) patients received monotherapy and 74 (36.10%) patients received combination therapy. The in-hospital mortality was significantly lower in patients administered appropriate therapy than inappropriate therapy (16.33% vs. 48.28%, p = 0.004); adjusted hazard ratio [HR] 0.55 [95% CI 0.35–0.84], p = 0.006). In-hospital mortality was also not different in combination therapy and monotherapy in the multivariate Cox regression analyses (adjusted HR 0.42 [95% CI 0.15–1.17], p = 0.096). However, combination therapy was associated with lower mortality than monotherapy in patients with sepsis or septic shock (adjusted HR 0.94 [95% CI 0.86–1.02], p = 0.047). Conclusions Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to Gram-negative pathogens. Combination therapy was associated with improved survival in patients with sepsis or septic shock. Clinicians need to choose optical empirical antimicrobials to improve survival outcomes in patients with BSIs. …

IntroductionIntravenous crystalloid fluid resuscitation forms a crucial part of the early intervention bundle for sepsis and septic shock, with the Surviving Sepsis Campaign guidelines recommending a 30 mL/kg fluid bolus within the first hour. Compliance with this suggested target varies in patients with comorbidities such as congestive heart failure, chronic kidney disease and cirrhosis due to concerns regarding iatrogenic fluid overload. However, it remains unclear whether resuscitation with higher fluid volumes puts them at greater risk of adverse outcomes. Thus, this systematic review will synthesise evidence from existing studies to assess the effects of a conservative as compared with a liberal approach to fluid resuscitation in patients at greater perceived risk of fluid overload due to comorbid conditions. Methods and analysisThis protocol was registered on PROSPERO and has been drafted following the checklist of Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will search MEDLINE, MEDLINE Epub Ahead of Print and In-Process, In-Data-Review & Other Non-Indexed Citations, Embase, Embase Classic, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Web of Science Core Collection, CINAHL Complete and ClinicalTrials.gov. A preliminary search of these databases was performed from their inception to 30 August 2022. The risk of bias and random errors will be assessed using the revised Cochrane risk-of-bias tool for randomised clinical trials and the Newcastle-Ottawa Scale for case–control and cohort studies. If a sufficient number of comparable studies are identified, we will perform a meta-analysis applying random effects model. We will investigate heterogeneity using a combination of visual inspection of the funnel plot as well as the Egger’s test. Ethics and disseminationNo ethics approval is required for this study since no original data will be collected. The findings will be disseminated through peer-reviewed publication and conference presentation. PROSPERO registration numberCRD42022348181. …

Given the potential benefits of shortened antibiotic courses, prior studies comparing shorter versus longer antibiotic courses have typically adopted a non-inferiority design [3,11]. However, in a study of critically ill patients in whom suboptimal treatment could result in death, a non-inferiority trial would pose a serious ethical dilemma – how to select an “acceptable” increased risk of mortality to use as a non-inferiority margin? For these reasons, we have designed a trial that requires shorter antibiotic therapy demonstrate superior clinical outcomes over longer antibiotic therapy, allowing partial/full credit to be awarded based on patient and clinicians’ perceptions of outcome importance and severity. Should clinical outcomes be comparable among the study arms, the DOOR/RADAR framework acknowledges potential unmeasured benefits of shorter courses (e.g., reduced costs, unmeasured toxicity, and antibiotic pressures selecting for individual and global microbial resistance) and accordingly assigns superiority to shorter antibiotic courses. The duration of antibiotic therapy reflected in this adjustment would be the actual (rather than assigned) duration, allowing for a pragmatic analysis of the interventions as applied in practice while mitigating differences between intention-to-treat and per-protocol analyses resulting from poor protocol adherence.

Abstract Background Little evidence exists regarding the prevalence of pathogens in bloodstream infections (BSIs), the mortality risk, and the benefit of combination therapy over monotherapy. This study aims to describe patterns of empiric antimicrobial therapy, and the epidemiology of Gram-negative pathogens, and to investigate the effect of appropriate therapy and appropriate combination therapy on the mortality of patients with BSIs. Methods This was a retrospective cohort study including all patients with BSIs of Gram-negative pathogens from January 2017 to December 2022 in a Chinese general hospital. The in-hospital mortality was compared between appropriate and inappropriate therapy, and between monotherapy and combination therapy for patients receiving appropriate therapy. We used Cox regression analysis to identify factors independently associated with in-hospital mortality. Results We included 205 patients in the study, of whom 147 (71.71%) patients received appropriate therapy compared with 58 (28.29%) who received inappropriate therapy. The most common Gram-negative pathogen was Escherichia coli (37.56%). 131 (63.90%) patients received monotherapy and 74 (36.10%) patients received combination therapy. The in-hospital mortality was significantly lower in patients administered appropriate therapy than inappropriate therapy (16.33% vs. 48.28%, p = 0.004); adjusted hazard ratio [HR] 0.55 [95% CI 0.35–0.84], p = 0.006). In-hospital mortality was also not different in combination therapy and monotherapy in the multivariate Cox regression analyses (adjusted HR 0.42 [95% CI 0.15–1.17], p = 0.096). However, combination therapy was associated with lower mortality than monotherapy in patients with sepsis or septic shock (adjusted HR 0.94 [95% CI 0.86–1.02], p = 0.047). Conclusions Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to Gram-negative pathogens. Combination therapy was associated with improved survival in patients with sepsis or septic shock. Clinicians need to choose optical empirical antimicrobials to improve survival outcomes in patients with BSIs. …

IMPORTANCE: The Surviving Sepsis Campaign recommends standard operating procedures for patients with sepsis. Real-world evidence about sepsis order set implementation is limited. OBJECTIVES: To estimate the effect of sepsis order set usage on hospital mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Fifty-four acute care hospitals in the United States from December 1, 2020 to November 30, 2022 involving 104,662 patients hospitalized for sepsis. MAIN OUTCOMES AND MEASURES: Hospital mortality. RESULTS: The sepsis order set was used in 58,091 (55.5%) patients with sepsis. Initial mean sequential organ failure assessment score was 0.3 lower in patients for whom the order set was used than in those for whom it was not used (2.9 sd [2.8] vs 3.2 [3.1], p < 0.01). In bivariate analysis, hospital mortality was 6.3% lower in patients for whom the sepsis order set was used (9.7% vs 16.0%, p < 0.01), median time from emergency department triage to antibiotics was 54 minutes less (125 interquartile range [IQR, 68–221] vs 179 [98–379], p < 0.01), and median total time hypotensive was 2.1 hours less (5.5 IQR [2.0–15.0] vs 7.6 [2.5–21.8], p < 0.01) and septic shock was 3.2% less common (22.0% vs 25.4%, p < 0.01). Order set use was associated with 1.1 fewer median days of hospitalization (4.9 [2.8–9.0] vs 6.0 [3.2–12.1], p < 0.01), and 6.6% more patients discharged to home (61.4% vs 54.8%, p < 0.01). In the multivariable model, sepsis order set use was independently associated with lower hospital mortality (odds ratio 0.70; 95% CI, 0.66–0.73). CONCLUSIONS AND RELEVANCE: In a cohort of patients hospitalized with sepsis, order set use was independently associated with lower hospital mortality. Order sets can impact large-scale quality improvement efforts.

American Journal of Respiratory and Critical Care Medicine, Volume 207, Issue 10, Page 1283-1299, May 15, 2023.

IntroductionUp to the present time, the laparoscopic approach for colon cancer is considered the gold standard. However, robotic surgery has been appraised in modern medicine. It is essential to evaluate the differences between laparoscopic and robotic surgery, owing to the significant impact they cause in postoperative morbidity and mortality. This article aims to perform a systematic review and meta-analysis of the literature to compare robotic versus laparoscopic colectomies in patients with colon cancer in terms of the incidence of colonic fistulas. Methods and analysisPubMed, Embase, Scopus, Web of Science, Science Direct, Cochrane Central Register of Controlled Trials, CINAHL, LILACS and Clinical trials databases will be searched for randomised clinical trials investigating the incidence of colonic fistulas in patients with colonic cancer, submitted to robotic surgery compared with a laparoscopic approach. No language or publication period restrictions will be imposed. The primary outcome will be the incidence of colonic fistulas in patients with colon cancer in different surgical approaches. The secondary outcomes will be the incidence of infection, sepsis, mortality, length of hospitalisation and malnutrition. Three independent reviewers will select the studies and extract data from the original publications. The risk of bias will be assessed using The Risk of Bias 2 tool, and the evidence’s certainty will be made using the Grading of Recommendations Assessment, Development and Evaluation. Data synthesis will be performed using the Review Manager software (RevMan V.5.2.3). To assess heterogeneity. We will compute the I2 statistics. In addition, a quantitative synthesis will be performed if the included studies are sufficiently homogeneous. Ethics and disseminationThis study will review the published data; thus, it is not necessary to obtain ethical approval. The findings of this systematic review will be published in a peer-reviewed journal. PROSPERO registration numberCRD42021295313. …

OBJECTIVES: The Surviving Sepsis Campaign Guidelines 2021 recommends that adult patients with sepsis requiring intensive care should be admitted to the ICU within 6 hours of their emergency department (ED) visits. However, there is limited evidence on whether 6 hours is the best target time for compliance with the sepsis bundle. We aimed to investigate the association between time from ED visits to ICU admission (i.e., ED length of stay [ED-LOS]) and mortality and identify the optimal ED-LOS for patients with sepsis. DESIGN: Retrospective cohort study. SETTING: The Medical Information Mart for Intensive Care Emergency Department and Medical Information Mart for Intensive Care IV databases. PATIENTS: Adult patients (≥ 18 yr old) who were transferred from the ED to the ICU and subsequently diagnosed with sepsis based on the Sepsis-3 criteria within 24 hours of ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1,849 patients with sepsis, we found a disproportionally higher mortality rate in patients immediately admitted to the ICU (e.g., < 2 hr). When using ED-LOS as a continuous variable, ED-LOS was not significantly associated with 28-day mortality (adjusted odds ratio [OR] per hour increase, 1.04; 95% CI, 0.96–1.13; p = 0.3) after an adjustment for potential confounders (e.g., demographics, triage vital signs, and laboratory results) in the multivariable analysis. However, when we categorized all patients into time quartiles (ED-LOS: < 3.3 hr, 3.3–4.5 hr, 4.6–6.1 hr, and > 6.1 hr), patients in the higher time quartiles (e.g., 3.3–4.5 hr) had higher 28-day mortality compared with those in the lowest time quartile (< 3.3 hr) (e.g., adjusted OR for patients in the second time quartile [3.3–4.5 hr] 1.59; 95% CI, 1.03–2.46; p = 0.04). CONCLUSIONS: Earlier admission to the ICU (e.g., within 3.3 hr of ED visits) was associated with lower 28-day mortality in patients with sepsis. Our findings suggest patients with sepsis who require intensive care may benefit from a more immediate ICU admission than 6 hours.

Objectives: To assess the association between levels of intensive care and in-hospital mortality in patients hospitalized for sepsis, stratified by Sequential Organ Failure Assessment (SOFA) score at admission. Design: A nationwide, propensity score-matched, retrospective cohort study. Setting: A Japanese national inpatient database with data on 70–75% of all ICU and high-dependency care unit (HDU) beds in Japan. Patients: Adult patients hospitalized for sepsis with SOFA scores greater than or equal to 2 on their day of admission between April 1, 2018, and March 31, 2021, were recruited. Propensity score matching was performed to compare in-hospital mortality, and patients were stratified into 10 groups according eto SOFA scores. Interventions: Two exposure and control groups according to treatment unit on day of admission: 1) ICU + HDU versus general ward and 2) ICU versus HDU. Measurements and Main Results: Of 97,070 patients, 19,770 (20.4%), 23,066 (23.8%), and 54,234 (55.9%) were treated in ICU, HDU, and general ward, respectively. After propensity score matching, the ICU + HDU group had significantly lower in-hospital mortality than the general ward group, among cohorts with SOFA scores greater than or equal to 6. There were no significant differences in in-hospital mortality among cohorts with SOFA scores 3–5. The ICU + HDU group had significantly higher in-hospital mortality than the general ward among cohorts with SOFA scores of 2. The ICU group had lower in-hospital mortality than the HDU group among cohorts with SOFA scores greater than or equal to 12. There were no significant differences in in-hospital mortality among cohorts with SOFA scores 5–11. The ICU group had significantly higher in-hospital mortality than the general ward group among cohorts with SOFA scores less than or equal to 4. Conclusions: Patients hospitalized for sepsis with SOFA scores greater than or equal to 6 in the ICU or HDU had lower in-hospital mortality than those in the general ward, as did those with SOFA scores greater than or equal to 12 in the ICU versus HDU.

No abstract available…

Abstract Background The early diagnosis of sepsis is hampered by the lack of reliable laboratory measures. There is growing evidence that presepsin and Mid-regional pro-adrenomedullin (MR-proADM) are promising biomarkers in the diagnosis of sepsis. This study was conducted to evaluate and compare the diagnostic value of MR-proADM and presepsin in sepsis patients. Methods We searched Web of Science, PubMed, Embase, China national knowledge infrastructure, and Wanfang up to 22th July, 2022, for studies evaluating the diagnosis performance of presepsin and MR-proADM in adult sepsis patients. Risk of bias was assessed using quadas-2. Pooled sensitivity and specificity were calculated using bivariate meta-analysis. Meta-regression and subgroup analysis were used to find source of heterogeneity. Results A total of 40 studies were eventually selected for inclusion in this meta-analysis, including 33 for presepsin and seven for MR-proADM. Presepsin had a sensitivity of 0.86 (0.82–0.90), a specificity of 0.79 (0.71–0.85), and an AUC of 0.90 (0.87–0.92). The sensitivity of MR-proADM was 0.84 (0.78–0.88), specificity was 0.86 (0.79–0.91), and AUC was 0.91 (0.88–0.93). The profile of control group, population, and standard reference may be potential sources of heterogeneity. Conclusions This meta-analysis demonstrated that presepsin and MR-proADM exhibited high accuracy (AUC ≥ 0.90) in the diagnosis of sepsis in adults, with MR-proADM showing significantly higher accuracy than presepsin. …

AbstractBackgroundThe northwestern border of Thailand is an area of low seasonal malaria transmission. Until recent successful malaria elimination activities, malaria was a major cause of morbidity and mortality. Historically the incidences of symptomatic Plasmodium falciparum and Plasmodium vivax malaria were approximately similar.MethodsAll malaria cases managed in the Shoklo Malaria Research Unit along the Thailand-Myanmar border between 2000 and 2016 were reviewed.ResultsThere were 80,841 consultations for symptomatic P. vivax and 94,467 for symptomatic P. falciparum malaria. Overall 4,844 (5.1%) patients with P. falciparum malaria were admitted to field hospitals, of whom 66 died, compared with 278 (0.34%) with P. vivax malaria, of whom four died (three were diagnosed with sepsis, so the contribution of malaria to their fatal outcomes is uncertain). Applying the 2015 “World Health Organization severe malaria criteria”, 68/80,841 (0.08%) of P. vivax and 1,482/94,467 (1.6%) of P. falciparum admissions were classified as severe. Overall, patients with P. falciparum malaria were 15 (95% CI 13.2-16.8) times more likely than P. vivax to require hospital admission, 19 (95% CI 14.6-23.8) times more likely to develop severe malaria, and at least 14 (95% CI 5.1-38.7) times more likely to die.ConclusionsIn this area both P. falciparum and P. vivax infections were important causes of hospitalization, but life-threatening P. vivax illness was rare.

by Thaer S. A. Abdalla, Rainer Grotelüschen, Ahmed S. A. Abdalla, Nathaniel Melling, Jakob R. Izbicki, Kai Bachmann Background Necrotizing fasciitis (NF) is a rare but lethal soft-tissue infection. There is still a paucity of information regarding the diagnostic tools and therapeutic strategies for the treatment of this devastating disease. This study aims to identify important perioperative parameters related to necrotizing fasciitis and to assess their relevance in terms of identifying NF. Methods and material We retrospectively analyzed patients who underwent surgical exploration for suspected necrotizing fasciitis at a tertiary referral center, to explore the clinical features and factors related to the presence of necrotizing fasciitis and mortality. Results Between 2010 and 2017, 88 patients underwent surgical exploration for suspected NF. The infection occurred in the lower extremities in 48 patients, in the thoracocervical region in 18 patients, and the perineum and abdomen in 22 patients. Histological evidence of NF was present in 59 of 88 patients. NF was associated with a longer hospital stay and ICU stay (p = 0.05 and 0.019 respectively) compared to patients without NF. ROC analysis showed that only macroscopic fascial appearance could discriminate patients with histological evidence of NF. Moreover, multivariate logistic regression revealed, that liver failure (p = 0.019), sepsis (p = 0.011), positive Gram stain (p = 0.032), and macroscopic fascial appearance (p…

Abstract Background Septic thrombophlebitis (STP) of the lower extremities caused by foreign bodies is rare in the clinic, and the symptoms are serious. If the correct treatment is not implemented as soon as possible, the patient may progress to sepsis. Case presentation We report the case of a 51-year-old normally healthy male who developed fever 3 days after field work. When he was weeding with a lawn mower in the field, a metal foreign body from the grass flew into his left lower abdomen, resulting in an eschar on his left lower abdomen. He was diagnosed with scrub typhus but did not respond well to anti-infective treatment. After a detailed inquiry of his medical history and an auxiliary examination, the diagnosis was confirmed as STP of the left lower limb caused by a foreign body. After surgery, anticoagulation and anti-infection treatment, the infection and thrombosis were controlled, and the patient was cured and discharged. Conclusions STP caused by foreign bodies is rare. Early detection of the aetiology of sepsis and early adoption of the correct measures can effectively block the progression of the disease and reduce the patient’s pain. Clinicians should identify the source of sepsis through a medical history and clinical examination. …

Objectives: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. Design: Multicenter, prospective, inception cohort study. Setting: Forty-four ICUs in 12 countries in four geographical regions. Subjects: Adult, acutely admitted ICU patients without a history of persistent/permanent AF or recent cardiac surgery were enrolled; inception periods were from October 2020 to June 2021. Interventions: None. Measurements and Main Results: We included 1,423 ICU patients and analyzed 1,415 (99.4%), among whom 221 patients had 539 episodes of AF. Most (59%) episodes were diagnosed with continuous electrocardiogram monitoring. The incidence of AF was 15.6% (95% CI, 13.8–17.6), of which newly developed AF was 13.3% (11.5–15.1). A history of arterial hypertension, paroxysmal AF, sepsis, or high disease severity at ICU admission was associated with AF. Used interventions to manage AF were fluid bolus 19% (95% CI 16–23), magnesium 16% (13–20), potassium 15% (12–19), amiodarone 51% (47–55), beta-1 selective blockers 34% (30–38), calcium channel blockers 4% (2–6), digoxin 16% (12–19), and direct current cardioversion in 4% (2–6). Patients with AF had more ischemic, thromboembolic (13.6% vs 7.9%), and severe bleeding events (5.9% vs 2.1%), and higher mortality (41.2% vs 25.2%) than those without AF. The adjusted cause-specific hazard ratio for 90-day mortality by AF was 1.38 (95% CI, 0.95–1.99). Conclusions: In ICU patients, AF occurred in one of six and was associated with different conditions. AF was associated with worse outcomes while not statistically significantly associated with 90-day mortality in the adjusted analyses. We observed variations in the diagnostic and management strategies for AF.

OBJECTIVES: The 2020 pediatric Surviving Sepsis Campaign (pSSC) recommends measuring lactate during the first hour of resuscitation for severe sepsis/shock. We aimed to improve compliance with this recommendation for patients who develop severe sepsis/shock while admitted to the PICU. DESIGN: Structured, quality improvement initiative. SETTING: Single-center, 26-bed, quaternary-care PICU. PATIENTS: All patients with PICU-onset severe sepsis/shock from December 2018 to December 2021. INTERVENTIONS: Creation of a multidisciplinary local sepsis improvement team, education program targeting frontline providers (nurse practitioners, resident physicians), and peer-to-peer nursing education program with feedback to key stakeholders. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was compliance with obtaining a lactate measurement within 60 minutes of the onset of severe sepsis/shock originating in our PICU using a local Improving Pediatric Sepsis Outcomes database and definitions. The process measure was time to first lactate measurement. Secondary outcomes included number of IV antibiotic days, number of vasoactive days, number of ICU days, and number of ventilator days. A total of 166 unique PICU-onset severe sepsis/shock events and 156 unique patients were included. One year after implementation of our first interventions with subsequent Plan-Do-Study-Act cycles, overall compliance increased from 38% to 47% (24% improvement) and time to first lactate decreased from 175 to 94 minutes (46% improvement). Using a statistical process control I chart, the preshift mean for time to first lactate measurement was noted to be 179 minutes and the postshift mean was noted to be 81 minutes demonstrating a 55% improvement. CONCLUSIONS: This multidisciplinary approach led to improvement in time to first lactate measurement, an important step toward attaining our target of lactate measurement within 60 minutes of septic shock identification. Improving compliance is necessary for understanding implications of the 2020 pSSC guidelines on sepsis morbidity and mortality.

Abstract Background Cryptosporidium is recognized as a significant pathogen of diarrhea disease in immunocompromised hosts, and studies have shown that Cryptosporidium infection is high in solid organ transplantation (SOT) patients and often has serious consequences. Because of the lack of specificity of diarrheasymptoms cased by Cryptosporidium infection, it is rarely reported in patients undergoing liver transplantation (LT). It frequently delays diagnosis, coming with severe consequences. In clinical work, diagnosing Cryptosporidium infection in LT patients is also complex but single, and the corresponding anti-infective treatment regimen has not yet been standardized. A rare case of septic shock due to a delayed diagnosis of Cryptosporidium infection after LT and relevant literature are discussed in the passage. Case presentation A patient who had received LT for two years was admitted to the hospital with diarrhea more than 20 days after eating an unclean diet. After failing treatment at a local hospital, he was admitted to Intensive Care Unit after going into septic shock. The patient presented hypovolemia due to diarrhea, which progressed to septic shock. The patient\'s sepsis shock was controlled after receiving multiple antibiotic combinations and fluid resuscitation. However, the persistent diarrhea, as the culprit of the patient\'s electrolyte disturbance, hypovolemia, and malnutrition, was unsolved. The causative agent of diarrhea, Cryptosporidium infection, was identified by colonoscopy, faecal antacid staining, and blood high-throughput sequencing (NGS). The patient was treated by reducing immunosuppression and Nitazoxanide (NTZ), which proved effective in this case. Conclusion When LT patients present with diarrhea, clinicians should consider the possibility of Cryptosporidium infection, in addition to screening for conventional pathogens. Tests such as colonoscopy, stool antacid staining and blood NGS sequencing can help diagnose and treat of Cryptosporidium infection early and avoid serious consequences of delayed diagnosis. In treating Cryptosporidium infection in LT patients, the focus should be on the patient\'s immunosuppressive therapy, striking a balance between anti-immunorejection and anti-infection should be sought. Based on practical experience, NTZ therapy in combination with controlled CD4 + T cells at 100–300/mm3 was highly effective against Cryptosporidium without inducing immunorejection. …

ObjectivesAlthough platelets have been linked to inflammatory development in sepsis, knowledge on their role as an indicator in sepsis treatment is scarce. Here, we investigated the association between time-dependent changes in platelet counts with mortality rates to reveal the role of platelets in sepsis therapy. DesignA retrospective cohort study. SettingWe screened the Medical Information Mart for Intensive Care (MIMIC-IV), a public database comprising data from critical care subjects at the Beth Israel Deaconess Medical Center (BIDMC) in Boston, Massachusetts, USA. ParticipantsA total of 7981 patients, who were admitted to the BIDMC between 2008 and 2019, were analysed based on Sepsis-3 criteria from MIMIC-IV. Primary and secondary outcome measuresPrimary and secondary outcomes included 30-day mortality after admission and length of intensive care unit (ICU) stay and hospitalisation, respectively. ResultsPatients with ≤10% reduction in proportion of platelet counts were associated with significantly lower 30-day mortality (14.1% vs 23.5%, p

Volume 14, Issue 1, December 2023 .

by Syeda Humaida Hasan, Jagadish Chandra Das, Kamrun Nahar, Muhammad Jabed Bin Amin Chowdhury, Tamanna Zahur, Mohammad Abu Faisal, Zabeen Choudhury, Dhiman Chowdhury Introduction Discharge against medical advice (DAMA) is an unexpected event for patients and healthcare personnel. The study aimed to assess the prevalence of DAMA in neonates along with characteristics of neonates who got DAMA and, causes and predictors of DAMA. Methods and findings This case-control study was carried out in Special Care Newborn Unit (SCANU) at Chittagong Medical College Hospital from July 2017 to December 2017. Clinical and demographic characteristics of neonates with DAMA were compared with that of discharged neonates. The causes of DAMA were identified by a semi-structured questionnaire. Predictors of DAMA were determined using a logistic regression model with a 95% confidence interval. A total of 6167 neonates were admitted and 1588 got DAMA. Most of the DAMA neonates were male (61.3%), term (74.7%), outborn (69.8%), delivered vaginally (65.7%), and had standard weight at admission (54.3%). A significant relationship (p < 0.001) was found between the variables of residence, place of delivery, mode of delivery, gestational age, weight at admission, and day and time of outcome with the type of discharge. False perceptions of wellbeing (28.7%), inadequate facilities for mothers (14.5%), and financial problems (14.1%) were the prevalent causes behind DAMA. Predictors of DAMA were preterm gestation (AOR 1.3, 95% CI 1.07–1.7, p = 0.013), vaginal delivery (AOR 1.56, 95% CI 1.31–1.86, p < 0.001), timing of outcome after office hours (AOR 477.15, 95% CI 236–964.6, p < 0.001), and weekends (AOR 2.55, 95% CI 2.06–3.17, p < 0.001). Neonates suffering from sepsis (AOR 1.4, 95% CI 1.1–1.7, p< 0.001), Respiratory Distress Syndrome (AOR 3.1, 95% CI 1.9–5.2, p< 0.001), prematurity without other complications (AOR 2.1, 95% CI 1.45–3.1, p < 0.001) or who were referred from north-western districts (AOR 1.48, 95% CI 1.13–1.95, p = 0.004) had higher odds for DAMA. Conclusions Identification of predictors and reasons behind DAMA may provide opportunities to improve the hospital environment and service related issues so that such vulnerable neonates can complete their treatment. We should ensure better communication with parents, provide provision for mothers’ corner, especially for outborn neonates, maintain a standard ratio of neonates and healthcare providers, and adopt specific DAMA policy by the hospital authority. …

ObjectivesIn the early stage of sepsis, identifying high-risk paediatric patients with a poor prognosis and providing timely and adequate treatment are critical. This study aimed to evaluate the effect of average body temperature within 24 hours of admission on the short-term prognosis of paediatric patients with sepsis. DesignA retrospective cohort study. SettingA single-centre, tertiary care hospital in China, containing patient data from 2010 to 2018. Participants1144 patients with sepsis were included. InterventionNone. Primary and secondary outcome measuresThe main outcome measure was in-hospital mortality, which was defined as death from any cause during hospitalisation. The secondary outcome was the length of hospital stay. ResultsThe LOWESS method showed a roughly ‘U’-shaped relationship between body temperature on the first day and in-hospital mortality. Multivariate logistic regression showed that severe hypothermia (OR 14.72, 95% CI 4.84 to 44.75), mild hypothermia (OR 3.71, 95% CI 1.26 to 10.90), mild hyperthermia (OR 3.41, 95% CI 1.17 to 9.90) and severe hyperthermia (OR 5.15, 95% CI 1.84 to 14.43) were independent risk factors for in-hospital mortality. Compared with other variables, the Wald 2 value of temperature on the first day minus the degree of freedom was the highest. ConclusionsWhether hypothermic or hyperthermic, the more abnormal the temperature on the first day is, the higher the risk of in-hospital death in children with sepsis. …

Objectives: The benefit of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing the occurrence rate of adverse cardiac and renal outcomes in patients with type 2 diabetes has been well described in randomized trials. Whether this benefit extends to patients at the most severe end of the disease spectrum requiring admission to the ICU remains to be examined. Design: Retrospective observational study. Setting: Data were obtained from a territory-wide clinical registry in Hong Kong (Clinical Data Analysis and Reporting System). Patients: All adult patients (age ≥ 18 yr) with type 2 diabetes and newly prescribed SGLT2 inhibitors or dipeptidyl peptidase-4 (DPP-4) inhibitors between January 1, 2015, and December 31, 2019. Interventions: None. Measurements and Main Results: After 1:2 propensity score matching, a total of 27,972 patients (10,308 SGLT2 inhibitors vs 17,664 DPP-4 inhibitors) were included in the final analysis. The mean age was 59 ± 11 years, and 17,416 (62.3%) were male. The median follow-up period was 2.9 years. The use of SGLT2 inhibitors was associated with decreased ICU admission (286 [2.8%] vs 645 [3.7%]; hazard ratio [HR], 0.79; 95% CI, 0.69–0.91; p = 0.001) and lower risks of all-cause mortality (315 [3.1%] vs 1,327 [7.5%]; HR, 0.44; 95% CI, 0.38–0.49; p < 0.001), compared with DPP-4 inhibitors. The severity of illness upon ICU admission by Acute Physiology and Chronic Health Evaluation IV-predicted risk of death was also lower in SGLT2 inhibitors users. Admissions and mortality due to sepsis were lower in SGLT2 inhibitor users compared with DPP-4 inhibitor users (admissions for sepsis: 45 [0.4%] vs 134 [0.8%]; p = 0.001 and mortality: 59 [0.6%] vs 414 [2.3%]; p < 0.001, respectively). Conclusions: In patients with type 2 diabetes, SGLT2 inhibitors were independently associated with lower rates of ICU admission and all-cause mortality across various disease categories.

Objectives: The Lessening Organ Dysfunction with Vitamin C trial showed a harmful effect of vitamin C on 28-day death or persistent organ dysfunction. To maximize interpretation, we present a post hoc Bayesian reanalysis. Design: Bayesian reanalysis of a randomized placebo-controlled trial. Setting: Thirty-five ICUs. Patients: Adults with proven or suspected infection, vasopressor support, and no more than 24 hours of ICU admission. Interventions: Patients were allocated to receive either vitamin C (50 mg/kg of body weight) or placebo every 6 hours for up to 96 hours. Measurements and Main Results: The primary outcome was the composite of death or persistent organ dysfunction (i.e., vasopressor use, invasive mechanical ventilation, or new renal replacement therapy) at 28 days. We used Bayesian log-binomial models with random effects for hospital site and varying informative prior beliefs for the effect of vitamin C to estimate risk ratios (RRs) with 95% credible intervals (Crls) in the intention to treat population (vitamin C, 435 patients; placebo, 437 patients). Using weakly neutral priors, patients allocated to vitamin C had a higher risk of death or persistent organ dysfunction at 28 days (RR, 1.20; 95% Crl, 1.04–1.39; probability of harm, 99%). This effect was consistent when using optimistic (RR, 1.14; 95% Crl, 1.00–1.31; probability of harm, 98%) and empiric (RR, 1.09; 95% Crl, 0.97–1.22; probability of harm, 92%) priors. Patients allocated to vitamin C also had a higher risk of death at 28 days under weakly neutral (RR, 1.17; 95% Crl, 0.98–1.40; probability of harm, 96%), optimistic (RR, 1.10; 95% Crl, 0.94–1.30; probability of harm, 88%), and empiric (RR, 1.05; 95% Crl, 0.92–1.19; probability of harm, 76%) priors. Conclusions: The use of vitamin C in adult patients with proven or suspected infection and vasopressor support is associated with high probability of harm.

American Journal of Respiratory and Critical Care Medicine, Volume 207, Issue 8, Page 1030-1041, April 15, 2023.

AbstractBackgroundSevere bacterial infections (SBI) in otherwise healthy children are rare and may represent an underlying impairment of the immune system including primary immunodeficiency (PID). However, it is unclear if and how children should be assessed.MethodsWe retrospectively analyzed data from hospital records of previously healthy children aged 3 days to 18 years with SBI including pleuropneumonia, meningitis, and/or sepsis. Patients were diagnosed or immunologically followed-up between 2013/01/01 and 2020/03/31.ResultsOut of 432 children with SBI, 360 children could be analyzed. Follow-up data were available for 265 (74%) children, of whom 244 children (92%) had immunological testing. Laboratory abnormalities were found in 51 of 244 patients (21%), with 3 deaths (1%). There were 14 (6%) children with immunodeficiency considered clinically relevant (3 complement deficiencies, 1 autoimmune neutropenia, 10 humoral immunodeficiencies) and 27 (11%) with milder humoral abnormalities or findings suggestive of delayed adaptive immune maturation.ConclusionsA substantial proportion of children with SBI may benefit from routine immunological testing, revealing (potentially) clinically relevant impaired immune function in 6-17% of children. The identification of immune abnormalities allows for specific counselling of families and optimization of preventive measures such as booster vaccinations to avoid future SBI episodes.

Abstract Background Bacillus cereus infections in immunocompetent patients are uncommon and mainly observed in fragile patients. It can cause lethal infections with multiple organ dysfunction syndrome (MODS). However, a patient presenting as venous sinus thrombosis and survival without sequela has not been reported. Case presentation A 20-year-old previously healthy male developed gastroenteritis after a meal, followed by fever, convulsions, and severe disturbance of consciousness. The patient had significant leukocytosis with a mildly elevated D-dimer, creatinine level, and respiratory failure. The CT(computed tomography) revealed fatal brain edema and subarachnoid hemorrhage. Previous blood culture in a local hospital revealed B. cereus, which was confirmed by mNGS(metagenomic next-generation sequencing) using blood and urine in our hospital. Accordingly, B. cereus sepsis with MODS were considered. Later, cerebral venous sinus thrombosis was proved. After anti-infection (linezolid 0.6 g, Q12h; and meropenem 1.0 g, Q8h), anti-coagulant (enoxaparin 6000U, Q12h), and other symptomatic treatments, the patient recovered completely without sequela at the 6-month follow-up. Conclusions This case suggests that in immunocompetent adults, there is still a risk of infection with B. cereus, causing severe MODS. Special attention should be paid to venous sinus thrombosis and subarachnoid hemorrhage in such cases, while, anti-coagulant is essential therapy. …

Worldwide maternal vaccination against group B Streptococcus (GBS), a pathogen that can cause morbidity and mortality in pregnant people and their infants, could avoid 214 300 cases of severe disease—which often present as meningitis and sepsis—in their children, as well as prevent 31 100 infant deaths, among other outcomes, according to estimates based on 140 million pregnant women from 183 countries.

ObjectiveThe important effect modifiers of high disease severity on the relationship between the different volumes of early fluid resuscitation and prognosis in septic patients are unknown. Thus, this study was designed to assess whether the efficacy of different volumes in the early fluid resuscitation treatment of sepsis is affected by disease severity. DesignRetrospective cohort study. SettingAdult intensive care unit (ICU) patients with sepsis from 2001 to 2012 in the MIMIC-III database. InterventionsThe intravenous fluid volume within 6 hours after the sepsis diagnosis serves as the primary exposure. The patients were divided into the standard (≥ 30 mL/kg) and restrict (<30 mL/kg) groups. Disease severity was defined by the sequential organ failure assessment (SOFA) score at ICU admission. Propensity score matching analysis was performed to ensure the robustness of our results. Primary and secondary outcome measuresThe primary endpoint of this study was 28-day mortality. Days without needing mechanical ventilation or vasopressor administration within 28-day of ICU admission serving as the secondary endpoint. ResultsIn total, 5154 consecutive individuals were identified in data analysis, 776 patients had a primary end-point event, 386 (49.68%) in the restrict group and 387 (49.81%) in the standard group. Compared with the restrict group, the standard group had higher 28-day mortality (adjusted HR, 1.32; 95% CI 1.03 to 1.70; p=0.03) in the subgroup with a sequential organ failure assessment (SOFA) score ≥10. By contrast, the risk of mortality reduction was modest in the subgroup with an SOFA score <10 (adjusted HR, 0.85; 95% CI 0.70 to 1.03; p=0.10). The effect of the interaction between the SOFA score and fluid resuscitation strategies on the 28-day mortality was significant (p=0.0035). ConclusionsHigh disease severity modifies the relationship between the volume of fluid resuscitation and mortality in patients with sepsis in the ICU; future studies investigating this interaction are warranted. …

Objectives: To describe frequency of positive blood cultures, patterns of pathogens’ characteristics and their resistance profile in patients with blood cultures drawn due to a presumed diagnosis of community-onset sepsis, and to examine the association between blood culture-positive pathogens and hospital mortality. Design: Retrospective cohort study. Setting: Two hundred one U.S. hospitals from 2016 to 2020 using the Premier Healthcare Database. Subjects: Adult patients presenting with community-onset sepsis who had blood cultures collected within 2 days of hospital admission. We defined sepsis using the U.S. Centers for Disease Control Adult Sepsis Event Surveillance criteria. Interventions: None. Measurements and Main Results: We identified 147,061 patients with community-onset sepsis. The number of blood culture-positive sepsis episodes was 21,167 (14%) and the number of nonblood culture-positive sepsis episodes was 20,326 (14%). Among patients with blood culture-positive sepsis, Gram-negative rods were isolated in 55% of patients, Gram-positive cocci were isolated in 47%. Of those, methicillin-resistant Staphylococcus aureus (MRSA) was 11%, ceftriaxone-resistant Enterobacterales/extended-spectrum β-lactamase was 7%, and carbapenem-resistant Enterobacterales was 1.3%. The crude in-hospital mortality was 17% for culture-negative sepsis, 13% for nonblood culture-positive sepsis, and 17% for blood culture-positive sepsis. In multilevel logistic regression models, compared with culture-negative sepsis, blood culture-positive sepsis (adjusted odds ratio [aOR], 0.89; 95% CI, 0.85–0.94) and nonblood culture-positive sepsis (aOR, 0.82; 95% CI, 0.78–0.87) were associated with lower odds of in-hospital mortality. Acinetobacter species, Pseudomonas aeruginosa, methicillin-sensitive Staphylococcus aureus, and MRSA were associated with higher in-hospital mortality, whereas Escherichia coli, Klebsiella species, Proteus species, and Streptococcus species were associated with lower in-hospital mortality. Conclusions: In patients hospitalized with community-onset sepsis, the prevalence of blood culture-positive sepsis was 14%. Among positive blood culture sepsis resistant organisms were infrequent. Compared with culture-negative sepsis, blood culture-positive sepsis and nonblood culture-positive sepsis were associated with lower in-hospital mortality.

Sepsis is caused by a dysregulated host response to infection (1) and is a major cause of morbidity and mortality with 11 million sepsis-related deaths worldwide annually, accounting for almost 20% of all deaths (2). A delayed efficacy antibiotic therapy is associated with poor outcome, particularly in patients with septic shock (3). Appropriate antibiotics could be defined as an antibiotic treatment that is effective against the identified bacteria, has the narrowest microbiological spectrum (4) and the optimal pharmacokinetic and pharmacodynamic (PK/PD) parameters to inhibit bacterial growth.

Abstract Background Bacillus cereus infections in immunocompetent patients are uncommon and mainly observed in fragile patients. It can cause lethal infections with multiple organ dysfunction syndrome (MODS). However, a patient presenting as venous sinus thrombosis and survival without sequela has not been reported. Case presentation A 20-year-old previously healthy male developed gastroenteritis after a meal, followed by fever, convulsions, and severe disturbance of consciousness. The patient had significant leukocytosis with a mildly elevated D-dimer, creatinine level, and respiratory failure. The CT(computed tomography) revealed fatal brain edema and subarachnoid hemorrhage. Previous blood culture in a local hospital revealed B. cereus, which was confirmed by mNGS(metagenomic next-generation sequencing) using blood and urine in our hospital. Accordingly, B. cereus sepsis with MODS were considered. Later, cerebral venous sinus thrombosis was proved. After anti-infection (linezolid 0.6 g, Q12h; and meropenem 1.0 g, Q8h), anti-coagulant (enoxaparin 6000U, Q12h), and other symptomatic treatments, the patient recovered completely without sequela at the 6-month follow-up. Conclusions This case suggests that in immunocompetent adults, there is still a risk of infection with B. cereus, causing severe MODS. Special attention should be paid to venous sinus thrombosis and subarachnoid hemorrhage in such cases, while, anti-coagulant is essential therapy. …

Abstract Background vasopressin is commonly used as a second-line vasopressor for patients with septic shock, but the optimal timing of initiation is uncertain. This study was designed to investigate when vasopressin initiation may be beneficial for 28-day mortality in septic shock patients. Methods This was a retrospective observational cohort study from the MIMIC-III v1.4 and MIMIC-IV v2.0 databases. All adults diagnosed with septic shock according to Sepsis-3 criteria were included. Patients were stratified into two groups based on norepinephrine (NE) dose at the time of vasopressin initiation, defined as the low doses of NE group (NE<0.25 µg/kg/min) and the high doses of NE group (NE ≥ 0.25 µg/kg/min). The primary end‐point was 28‐day mortality after diagnosis of septic shock. The analysis involved propensity score matching (PSM), multivariable logistic regression, doubly robust estimation, the gradient boosted model, and an inverse probability‐weighting model. Results A total of 1817 eligible patients were included in our original cohort (613 in the low doses of NE group and 1204 in the high doses of NE group). After 1:1 PSM, 535 patients from each group with no difference in disease severity were included in the analysis. The results showed that vasopressin initiation at low doses of NE was associated with reduced 28-day mortality (odds ratio [OR] 0.660, 95% confidence interval [CI] 0.518–0.840, p < 0.001). Compared with patients in the high doses of NE group, patients in the low doses of NE group received significantly shorter duration of NE, with less intravenous fluid volume on the first day after initiation of vasopressin, more urine on the second day, and longer mechanical ventilation-free days and CRRT-free days. Nevertheless, there were no significant differences in hemodynamic response to vasopressin, duration of vasopressin, and ICU or hospital length of stay. Conclusions Among adults with septic shock, vasopressin initiation when low-dose NE was used was associated with an improvement in 28-day mortality. …

IntroductionSepsis, the leading cause of acute kidney injury (AKI), is associated with a high morbidity and mortality. Alkaline phosphatase (ALP) is an endogenous detoxifying enzyme. A recombinant human ALP compound, ilofotase alfa, showed no safety or tolerability concerns in a phase 2 trial. Renal function improvement over 28 days was significantly greater in the ilofotase alfa group. Moreover, a significant relative reduction in 28-day all-cause mortality of >40% was observed. A follow-up trial has been designed to confirm these findings. Methods and analysisThis is a phase 3, global, multi-centre, randomised, double-blind, placebo-controlled, sequential design trial in which patients are randomly assigned to either placebo or 1.6 mg/kg ilofotase alfa. Randomisation is stratified by baseline modified Sequential Organ Failure Assessment (mSOFA) score and trial site. The primary objective is to confirm the survival benefit with ilofotase alfa by demonstrating a reduction in 28-day all-cause mortality in patients with sepsis-associated AKI requiring vasopressors. A maximum of 1400 patients will be enrolled at ~120 sites in Europe, North America, Japan, Australia and New Zealand. Up to four interim analyses will take place. Based on predefined decision rules, the trial may be stopped early for futility or for effectiveness. In addition, patients with COVID-19 disease and patients with ‘moderate to severe’ chronic kidney disease are analysed as 2 separate cohorts of 100 patients each. An independent Data Monitoring Committee evaluates safety data at prespecified intervals throughout the trial. Ethics and disseminationThe trial is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Results of this study will determine the potential of ilofotase alfa to reduce mortality in critically ill patients with sepsis-associated AKI and will be published in a peer-reviewed scientific journal. Trial registration numberEudraCT CT Number 2019-0046265-24. US IND Number 117 605 Pre-results. ClinicalTrials.gov number: NCT04411472. …

Abstract Background Previous studies have been inconclusive about racial disparities in sepsis. This study evaluated the impact of ethnic background on management and outcome in sepsis and septic shock. Methods This analysis included 17,146 patients suffering from sepsis and septic shock from the multicenter eICU Collaborative Research Database. Generalized estimated equation (GEE) population-averaged models were used to fit three sequential regression models for the binary primary outcome of hospital mortality. Results Non-Hispanic whites were the predominant group (n = 14,124), followed by African Americans (n = 1,852), Hispanics (n = 717), Asian Americans (n = 280), Native Americans (n = 146) and others (n = 830). Overall, the intensive care treatment and hospital mortality were similar between all ethnic groups. This finding was concordant in patients with septic shock and persisted after adjusting for patient-level variables (age, sex, mechanical ventilation, vasopressor use and comorbidities) and hospital variables (teaching hospital status, number of beds in the hospital). Conclusion We could not detect ethnic disparities in the management and outcomes of critically ill septic patients and patients suffering from septic shock. Disparate outcomes among critically ill septic patients of different ethnicities are a public health, rather than a critical care challenge. …

American Journal of Respiratory and Critical Care Medicine, Volume 207, Issue 7, Page 853-854, April 1, 2023.

Abstract Background There is a growing interest in Klebsiella variicola as a causative pathogen in humans, though its clinical features and the impact of co-infection or secondary infection with COVID-19 remain unknown. Case presentation A 71-year-old man presented with fever, altered mental status and generalized weakness and was admitted to ICU due to severe COVID-19 pneumonia. He was newly diagnosed with type II diabetes mellitus upon admission. On hospital day 3, his respiratory status deteriorated, requiring invasive mechanical ventilation. On hospital day 10, superimposed bacterial pneumonia was suspected and subsequently, broad-spectrum antibiotics were administered for the associated bloodstream infection. On hospital day 13, despite administration of active antibiotics and appropriate source control, he decompensated and died. The causative organism isolated from blood cultures was initially reported as K. pneumoniae, but it was identified as K. variicola by a genetic analysis. A representative isolate (FUJ01370) had a novel multilocus sequence typing allelic profile (gapA-infB-mdh-pgi-phoE-rpoB-tonB: 16-24-21-27-52-17-152), to which sequence type 5794 was assigned (GenBank assembly accession: GCA_019042755.1). Conclusions We report a fatal case of respiratory and bloodstream infection due to K. variicola complicating severe COVID-19. Co-infection or secondary infection of K. variicola in COVID-19 is likely under-recognized and can be fulminant as in this case. …

OBJECTIVES: Perturbed host metabolism is increasingly recognized as a pillar of sepsis pathogenesis, yet the dynamic alterations in metabolism and its relationship to other components of the host response remain incompletely understood. We sought to identify the early host-metabolic response in patients with septic shock and to explore biophysiological phenotyping and differences in clinical outcomes among metabolic subgroups. DESIGN: We measured serum metabolites and proteins reflective of the host-immune and endothelial response in patients with septic shock. SETTING: We considered patients from the placebo arm of a completed phase II, randomized controlled trial conducted at 16 U.S. medical centers. Serum was collected at baseline (within 24 hr of the identification of septic shock), 24-hour, and 48-hour postenrollment. Linear mixed models were built to assess the early trajectory of protein analytes and metabolites stratified by 28-day mortality status. Unsupervised clustering of baseline metabolomics data was conducted to identify subgroups of patients. PATIENTS: Patients with vasopressor-dependent septic shock and moderate organ dysfunction that were enrolled in the placebo arm of a clinical trial. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-one metabolites and 10 protein analytes were measured longitudinally in 72 patients with septic shock. In the 30 patients (41.7%) who died prior to 28 days, systemic concentrations of acylcarnitines and interleukin (IL)-8 were elevated at baseline and persisted at T24 and T48 throughout early resuscitation. Concentrations of pyruvate, IL-6, tumor necrosis factor-α, and angiopoietin-2 decreased at a slower rate in patients who died. Two groups emerged from clustering of baseline metabolites. Group 1 was characterized by higher levels of acylcarnitines, greater organ dysfunction at baseline and postresuscitation (p < 0.05), and greater mortality over 1 year (p < 0.001). CONCLUSIONS: Among patients with septic shock, nonsurvivors exhibited a more profound and persistent dysregulation in protein analytes attributable to neutrophil activation and disruption of mitochondrial-related metabolism than survivors.

IntroductionThe ProSPoNS trial is a multicentre, double-blind, placebo-controlled trial to evaluate the role of probiotics in prevention of neonatal sepsis. The present protocol describes the data and methodology for the cost utility of the probiotic intervention alongside the controlled trial. Methods and analysisA societal perspective will be adopted in the economic evaluation. Direct medical and non-medical costs associated with neonatal sepsis and its treatment would be ascertained in both the intervention and the control arm. Intervention costs will be facilitated through primary data collection and programme budgetary records. Treatment cost for neonatal sepsis and associated conditions will be accessed from Indian national costing database estimating healthcare system costs. A cost–utility design will be employed with outcome as incremental cost per disability-adjusted life year averted. Considering a time-horizon of 6 months, trial estimates will be extrapolated to model the cost and consequences among high-risk neonatal population in India. A discount rate of 3% will be used. Impact of uncertainties present in analysis will be addressed through both deterministic and probabilistic sensitivity analysis. Ethics and disseminationHas been obtained from EC of the six participating sites (MGIMS Wardha, KEM Pune, JIPMER Puducherry, AIPH, Bhubaneswar, LHMC New Delhi, SMC Meerut) as well as from the ERC of LSTM, UK. A peer-reviewed article will be published after completion of the study. Findings will be disseminated to the community of the study sites, with academic bodies and policymakers. RegistrationThe protocol has been approved by the regulatory authority (Central Drugs Standards Control Organisation; CDSCO) in India (CT-NOC No. CT/NOC/17/2019 dated 1 March 2019). The ProSPoNS trial is registered at the Clinical Trial Registry of India (CTRI). Registered on 16 May 2019. Trial registration numberCTRI/2019/05/019197; Clinical Trial Registry. …

by Naoya Kawanoue, Kosuke Kuroda, Hiroko Yasuda, Masahiko Oiwa, Satoshi Suzuki, Hidenori Wake, Hiroki Hosoi, Masahiro Nishibori, Hiroshi Morimatsu, on behalf of the Okayama Research Investigation Organizing Network (ORION) Background Few sepsis biomarkers accurately predict severity and mortality. Previously, we had reported that first-day histidine-rich glycoprotein (HRG) levels were significantly lower in patients with sepsis and were associated with mortality. Since the time trends of HRG are unknown, this study focused on the time course of HRG in patients with sepsis and evaluated the differences between survivors and non-survivors. Methods A multicenter prospective observational study was conducted involving 200 patients with sepsis in 16 Japanese hospitals. Blood samples were collected on days 1, 3, 5, and 7, and 28-day mortality was used for survival analysis. Plasma HRG levels were determined using a modified quantitative sandwich enzyme-linked immunosorbent assay. Results First-day HRG levels in non-survivors were significantly lower than those in survivors (mean, 15.7 [95% confidence interval (CI), 13.4–18.1] vs 20.7 [19.5–21.9] μg/mL; P = 0.006). Although there was no time × survivors/non-survivors interaction in the time courses of HRG (P = 0.34), the main effect of generalized linear mixed models was significant (P < 0.001). In a univariate Cox proportional hazards model with each variable as a time-dependent covariate, higher HRG levels were significantly associated with a lower risk of mortality (hazard ratio, 0.85 [95% CI, 0.78–0.92]; P < 0.001). Furthermore, presepsin levels (P = 0.02) and Sequential Organ Function Assessment scores (P < 0.001) were significantly associated with mortality. Harrell’s C-index values for the 28-day mortality effect of HRG, presepsin, procalcitonin, and C-reactive protein were 0.72, 0.70, 0.63, and 0.59, respectively. Conclusions HRG levels in non-survivors were consistently lower than those in survivors during the first seven days of sepsis. Repeatedly measured HRG levels were significantly associated with mortality. Furthermore, the predictive power of HRG for mortality may be superior to that of other singular biomarkers, including presepsin, procalcitonin, and C-reactive protein. …

When Laura Lambert started to feel ill on Feb 5, 2017, she thought it was the beginning of a flu infection. She had no idea that it was, in fact, pneumococcal septicaemia and she was about to face the fight of her life—a fight she very nearly lost.

A severe type of mpox in people with advanced HIV is characterized by necrotizing skin lesions, lung nodules, and acute infections, including sepsis, according to an analysis of 382 hospitalized patients from 19 countries published in The Lancet. This form of mpox carries a high mortality rate for those with low levels of a type of white blood cell called CD4 T lymphocytes or CD4 cells: of the 179 cases the researchers analyzed with 200 or fewer CD4 cells per mm3, 27 people—or 15%—died.

IntroductionEarly recognition and appropriate management of paediatric sepsis are known to improve outcomes. A previous system’s biology investigation of the systemic immune response in neonates to sepsis identified immune and metabolic markers that showed high accuracy for detecting bacterial infection. Further gene expression markers have also been reported previously in the paediatric age group for discriminating sepsis from control cases. More recently, specific gene signatures were identified to discriminate between COVID-19 and its associated inflammatory sequelae. Through the current prospective cohort study, we aim to evaluate immune and metabolic blood markers which discriminate between sepses (including COVID-19) from other acute illnesses in critically unwell children and young persons, up to 18 years of age.Methods and analysisWe describe a prospective cohort study for comparing the immune and metabolic whole-blood markers in patients with sepsis, COVID-19 and other illnesses. Clinical phenotyping and blood culture test results will provide a reference standard to evaluate the performance of blood markers from the research sample analysis. Serial sampling of whole blood (50 μL each) will be collected from children admitted to intensive care and with an acute illness to follow time dependent changes in biomarkers. An integrated lipidomics and RNASeq transcriptomics analyses will be conducted to evaluate immune-metabolic networks that discriminate sepsis and COVID-19 from other acute illnesses. This study received approval for deferred consent.Ethics and disseminationThe study has received research ethics committee approval from the Yorkshire and Humber Leeds West Research Ethics Committee 2 (reference 20/YH/0214; IRAS reference 250612). Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites.Trial registration numberNCT04904523.…

ObjectivesTo identify the clinical risk factors that influence in-hospital mortality in elderly patients with persistent sepsis-associated acute kidney injury (S-AKI) and to establish and validate a nomogram to predict in-hospital mortality.DesignRetrospective cohort analysis.SettingData from critically ill patients at a US centre between 2008 and 2021 were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database (V.1.0).ParticipantsData from 1519 patients with persistent S-AKI were extracted from the MIMIC-IV database.Primary outcomeAll-cause in-hospital death from persistent S-AKI.ResultsMultiple logistic regression revealed that gender (OR 0.63, 95% CI 0.45–0.88), cancer (2.5, 1.69–3.71), respiratory rate (1.06, 1.01–1.12), AKI stage (2.01, 1.24–3.24), blood urea nitrogen (1.01, 1.01–1.02), Glasgow Coma Scale score (0.75, 0.70–0.81), mechanical ventilation (1.57, 1.01–2.46) and continuous renal replacement therapy within 48 hours (9.97, 3.39–33.9) were independent risk factors for mortality from persistent S-AKI. The consistency indices of the prediction and the validation cohorts were 0.780 (95% CI: 0.75–0.82) and 0.80 (95% CI: 0.75–0.85), respectively. The model’s calibration plot suggested excellent consistency between the predicted and actual probabilities.ConclusionsThis study’s prediction model demonstrated good discrimination and calibration abilities to predict in-hospital mortality of elderly patients with persistent S-AKI, although it warrants further external validation to verify its accuracy and applicability.…

IntroductionThe efficacy of taurolidine containing lock solutions for the prevention of central line-associated bloodstream infections (CLABSI) in paediatric oncology patients is still unknown. If the taurolidine-citrate-heparin lock appears to decrease the incidence of CLABSIs, we hope to increase the quality of life of children with cancer by subsequently reducing the central venous access device (CVAD)-removal rates, dispense of antibiotics, hospital admissions and incidence of severe sepsis resulting in intensive care unit admission.Methods and analysisThis assessor-blinded randomised controlled trial including 462 patients was designed to compare the taurolidine-citrate-heparin lock to the heparin-only lock for the prevention of CLABSIs in paediatric oncology patients. Patients receiving their first CVAD at the Princess Máxima Centre for Paediatric Oncology, Utrecht, the Netherlands, are eligible for inclusion. The primary outcome of this study is the incidence of first CLABSIs from CVAD insertion until the end of the study, maximum follow-up of 90 days. An intention-to-treat and a per-protocol analysis will be performed. An interim analysis will be performed after the inclusion of 50% of the patients. The results of the interim analysis and overall conduct of the trial will be discussed by a data safety monitoring board.Ethics and disseminationThe medical ethics committee NedMec, Utrecht, the Netherlands, has approved this research (number 20/370). Written informed consent for participation in this trial and publication of the trial data is obtained from all patients and/or their parents/guardians. The results of this trial will be published in a peer-reviewed journal and the data will be made available on reasonable request after publication of the main results manuscript.Trial registration numbersNTR6688; NCT05740150.…

fHbp is a virulence factor expressed by the human-specific pathogen N. meningitidis, a leading cause of meningitis and sepsis worldwide which frequently asymptomatically colonizes the human upper airway. fHbp binds human CFH, a negative regulator of the complement system, and has multiple roles during meningococcal infection. fHbp was initially identified as a vaccine antigen, named GNA1870 [1] or LP2086 [2]. It was then shown that the meningococcus binds CFH to its surface via an ~33 kDa protein, promoting bacterial survival in serum [3].

ObjectivesTo identify the association between maternal SARS-CoV-2 infection in pregnancy and individual neonatal morbidities and outcomes, particularly longer-term outcomes such as neurodevelopment.DesignSystematic review of outcomes of neonates born to pregnant women diagnosed with a SARS-CoV-2 infection at any stage during pregnancy, including asymptomatic women.Data sourcesMEDLINE, Embase, Global Health, WHOLIS and LILACS databases, last searched on 28 July 2021.Eligibility criteriaCase–control and cohort studies published after 1 January 2020, including preprint articles were included. Study outcomes included neonatal mortality and morbidity, preterm birth, caesarean delivery, small for gestational age, admission to neonatal intensive care unit, level of respiratory support required, diagnosis of culture-positive sepsis, evidence of brain injury, necrotising enterocolitis, visual or hearing impairment, neurodevelopmental outcomes and feeding method. These were selected according to a core outcome set.Data extraction and synthesisData were extracted into Microsoft Excel by two researchers, with statistical analysis completed using IBM SPSS (Version 27). Risk of bias was assessed using a modified Newcastle-Ottawa Scale.ResultsThe search returned 3234 papers, from which 204 were included with a total of 45 646 infants born to mothers with SARS-CoV-2 infection during pregnancy across 36 countries. We found limited evidence of an increased risk of some neonatal morbidities, including respiratory disease. There was minimal evidence from low-income settings (1 study) and for neonatal outcomes following first trimester infection (17 studies). Neonatal mortality was very rare. Preterm birth, neonatal unit admission and small for gestational age status were more common in infants born following maternal SARS-CoV-2 infection in pregnancy in most larger studies.ConclusionsThere are limited data on neonatal morbidity and mortality following maternal SARS-CoV-2 infection, particularly from low-income countries and following early pregnancy infections. Large, representative studies addressing these outcomes are needed to understand the consequences for babies born to women with SARS-CoV-2.PROSPERO registration numberCRD42021249818.…