Search

Sepsis is a heterogeneous syndrome and phenotypes have been proposed using clinical data. Less is known about the contribution of protein biomarkers to clinical sepsis phenotypes and their importance for treatment effects in randomized trials of resuscitation. The objective is to use both clinical and biomarker data in the Protocol-Based Care for Early Septic Shock (ProCESS) randomized trial to determine sepsis phenotypes and to test for heterogeneity of treatment effect by phenotype comparing usual care to protocolized early, goal-directed therapy(EGDT). In this secondary analysis of a subset of patients with biomarker sampling in the ProCESS trial (n = 543), we identified sepsis phenotypes prior to randomization using latent class analysis of 20 clinical and biomarker variables. Logistic regression was used to test for interaction between phenotype and treatment arm for 60-day inpatient mortality. Among 543 patients with severe sepsis or septic shock in the ProCESS trial, a 2-class model best fit the data (p = 0.01). Phenotype 1 (n = 66, 12%) had increased IL-6, ICAM, and total bilirubin and decreased platelets compared to phenotype 2 (n = 477, 88%, p

INTRODUCTION: Sepsis is a major cause of morbidity and mortality worldwide. In the updated, 2016 Sepsis-3 criteria, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, where organ dysfunction can be represented by an increase in the Sequential Organ Failure Assessment (SOFA) score of 2 points or more. We sought to apply the Sepsis-3 criteria to characterise the septic cohort in the Amsterdam University Medical Centres database (Amsterdam UMCdb). METHODS: We examined adult intensive care unit (ICU) admissions in the Amsterdam UMCdb, which contains de-identified data for patients admitted to a mixed surgical-medical ICU at a tertiary academic medical centre in the Netherlands. We operationalised the Sepsis-3 criteria, defining organ dysfunction as an increase in the SOFA score of 2 points or more, while infection was defined as a new course of antibiotics or an escalation in antibiotic therapy, with at least one antibiotic given intravenously. Patients with sepsis were determined to be in septic shock if they additionally required the use of vasopressors and had a lactate level >2 mmol/L. RESULTS: We identified 18,221 ICU admissions from 16,408 patients in our cohort. There were 6,312 unique sepsis episodes, of which 30.2% met the criteria for septic shock. A total of 4,911/6,312 sepsis (77.8%) episodes occurred on ICU admission. Forty-seven percent of emergency medical admissions and 36.7% of emergency surgical admissions were for sepsis. Overall, there was a 12.5% ICU mortality rate; patients with septic shock had a higher ICU mortality rate (38.4%) than those without shock (11.4%). CONCLUSIONS: We successfully operationalised the Sepsis-3 criteria to the Amsterdam UMCdb, allowing the characterization and comparison of sepsis epidemiology across different centres.

The lactate to albumin ratio (LAR) has been associated with the severity and outcome of critical illness and sepsis. However, there are no studies on the kinetics of the LAR during the early phase of sepsis. Therefore, we aimed to investigate the LAR and its kinetics in critically ill patients with new onset sepsis regarding the severity and outcome of sepsis. We prospectively enrolled 102 patients with sepsis or septic shock within 48 h from diagnosis. LARs were recorded at inclusion in the study and one week later. Patients were followed for 28 days. LAR was significantly lower one week after enrollment compared to baseline in all patients (p < 0.001). LARs were significantly higher in patients with septic shock and in nonsurvivors compared to patients with sepsis and survivors, respectively, both at inclusion (p < 0.001, p < 0.001) and at one week later (p < 0.001, p < 0.001). LARs at baseline were positively associated with the severity of sepsis (APACHE II: r = 0.29, p = 0.003; SOFA: r = 0.33, p < 0.001) and inflammatory biomarkers, such as C-reactive protein (r = 0.29, p < 0.1), procalcitonin (r = 0.47, p < 0.001), interleukin 6 (r = 0.28, p = 0.005) interleukin 10 (r = 0.3, p = 0.002) and suPAR (r = 0.28, p = 0.004). In addition, a higher LAR, but not its kinetics, was an independent predictor of 28-day mortality (at inclusion: HR 2.27, 95% C.I. 1.01–5.09, p = 0.04; one week later: HR: 4.29, 95% C.I. 1.71–10.78, p = 0.002). In conclusion, the LAR may be a valuable prognostic indicator in critically ill patients with sepsis at admission and one week later. [ABSTRACT FROM AUTHOR]

Purpose: Septic arthritis is a dangerous medical condition requiring prompt diagnosis, often via arthrocentesis. A "dry tap" occurs when no fluid is aspirated. We hypothesized that the absence of a joint effusion on pre-procedure advanced imaging would reliably predict a dry tap and exclude septic arthritis. Methods: A cohort of 217 arthrocentesis cases of large joints (hips, shoulders, knees) from our institution, with pre-procedure advanced imaging (CT, MR, US) of the same joint performed within the previous 48 h, was analyzed. Exclusion criteria included non-native joints or inadequate imaging of the affected joint. These cases underwent blinded review by 4 radiologists who measured the deepest pocket of joint fluid on the pre-procedure imaging. Wilcoxon rank-sum test was performed comparing joint fluid pocket size to outcomes of successful aspiration and final diagnosis. Results: A smaller average joint pocket fluid size was present on advanced imaging in both dry taps compared with successful arthrocenteses (p <.0001), and in uninfected joints compared with septic joints (p =.0001). However, the overlap of values was too great to allow for a perfectly predictive cutoff. 29% (5/17) of patients with no visible joint fluid on pre-aspiration imaging underwent successful arthrocentesis, one case representing septic arthritis. Conclusion: Volume of joint fluid on advanced pre-arthrocentesis imaging cannot reliably predict subsequent dry tap nor exclude septic arthritis. [ABSTRACT FROM AUTHOR]

Objective To explore the curative effect of hydrocortisone ascorbic acid, vitamin C and vitamin B1 (HAT) therapy on septic shock and its influence on the time of vasoactive drug application, hemodynamic parameters and shortterm prognosis. Methods According to different treatment plans, 92 patients with septic shock were divided into the HAT group and the routine treatment group, 46 cases in each group. The routine treatment group was given routine treatments [anti-infection, fluid replacement, stabling blood pressure and continuous renal replacement therapy (CRRT)], while the HAT group was additionally given HAT therapy. All patients were treated continuously for 3 d. The indexes related the curative effect, scores of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA), levels of mean arterial pressure (MAP), heart rate (HR), central arterial pressure (CAP), D-lactic acid (D-Lac), creatinine (Cr), hypersensitive C-reactive protein (hs-CRP) and procalcitonin (PCT) before and after treatment, incidence of adverse reactions and 28 d survival rate by follow-up were compared between the two groups. Results The circulation stabilization time, use time of vasoactive drugs and hormones, mechanical ventilation time, CRRT time, treatment time in ICU and total hospitalization time were shorter in the HAT group than those in the routine treatment group (P＜0.05). After 7 d of treatment, scores of APACHE Ⅱand SOFA, levels of HR, D-Lac, Cr, hs-CRP and PCT were lower in the HAT group than those in the routine treatment group, while MAP and CAP were higher than those in the routine treatment group (P＜0.05). The 28-day survival rate was 65.22% in the HAT group, which was higher than that in the routine treatment group (45.65%, P＜0.05). Conclusion HAT therapy can improve clinical curative effect in patients with septic shock, shorten use time of vasoactive drugs, improve hemodynamic parameters and short-term prognosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: Septic shock is a potentially life-threatening condition. The aim of this study was to identify clinical and epidemiological factors associated with mortality in pediatric patients admitted to a pediatric intensive care unit (PICU) with septic shock. Materials and methods: A retrospective comparative case series study was conducted with children aged 1 month to 14 years with septic shock from 2018 to 2020 in a PICU in Lima, Peru. Patients were divided into deceased and survivor groups based on their condition at discharge from the PICU. The influence of each variable on mortality was assessed using a logistic regression model. Results: A total of 174 patients were included in the study, with 51 (29.3%) fatalities. Deceased patients, compared to survivors, were older, had a higher incidence of oncological disease (31.4% vs. 14.6%; p = 0.011), more frequently presented with hemoglobin = 9 g/dL (44% vs. 28%; p = 0.043), lactate > 2 mmol/L (70% vs. 44%; p = 0.002), platelets = 150 (×103)/µL (77% vs. 42%; p < 0.001), and pH = 7.1 (31% vs. 6%; p < 0.001). In the logistic regression model, factors related to mortality were having a pH = 7.1 (odds ratio [OR] = 8.95; 95% confidence interval [CI]: 2.52-31.75) and platelets = 150 (×103)/µL (OR = 3.89; 95% CI: 1.40-10.84). Conclusions: Factors associated with mortality in pediatric patients with septic shock were a pH = 7.1 and platelets = 150 (×103)/µL in the assessments conducted upon admission to the PICU. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate real-world implications of updated Surviving Sepsis Campaign (SSC) recommendations for antibiotic timing. DESIGN: Retrospective cohort study. SETTING: Twelve hospitals in the Southeastern United States between 2017 and 2021. PATIENTS: One hundred sixty-six thousand five hundred fifty-nine adult hospitalized patients treated in the emergency department for suspected serious infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We determined the number and characteristics of patients affected by updated SSC recommendations for initiation of antibiotics that incorporate a risk- and probability-stratified approach. Using an infection prediction model with a cutoff of 0.5 to classify possible vs. probable infection, we found that 30% of the suspected infection cohort would be classified as shock absent, possible infection and thus eligible for the new 3-hour antibiotic recommendation. In real-world practice, this group had a conservative time to antibiotics (median, 5.5 hr; interquartile range [IQR], 3.2-9.8 hr) and low mortality (2%). Patients categorized as shock absent, probable infection had a median time to antibiotics of 3.2 hours (IQR, 2.1-5.1 hr) and mortality of 3%. Patients categorized as shock present, the probable infection had a median time to antibiotics 2.7 hours (IQR, 1.7-4.6 hr) and mortality of 17%, and patients categorized as shock present, the possible infection had a median time to antibiotics 6.9 hours (IQR, 3.5-16.3 hr) and mortality of 12%. CONCLUSIONS: These data support recently updated SSC recommendations to align antibiotic timing targets with risk and probability stratifications. Our results provide empirical support that clinicians and hospitals should not be held to 1-hour targets for patients without shock and with only possible sepsis. [ABSTRACT FROM AUTHOR]

BACKGROUND: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. METHODS: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. RESULTS: Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2-161.5], p = 0.0028). Similarly, oxygenation index decreased by - 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus - 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI - 8.6 to - 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5-47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. CONCLUSIONS: In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

BACKGROUND: Sepsis is a highly heterogeneous syndrome, which has hindered the development of effective therapies. This has prompted investigators to develop a precision medicine approach aimed at identifying biologically homogenous subgroups of patients with septic shock and critical illnesses. Transcriptomic analysis can identify subclasses derived from differences in underlying pathophysiological processes that may provide the basis for new targeted therapies. The goal of this study was to elucidate pathophysiological pathways and identify pediatric septic shock subclasses based on whole blood RNA expression profiles. METHODS: The subjects were critically ill children with cardiopulmonary failure who were a part of a prospective randomized insulin titration trial to treat hyperglycemia. Genome-wide expression profiling was conducted using RNA sequencing from whole blood samples obtained from 46 children with septic shock and 52 mechanically ventilated noninfected controls without shock. Patients with septic shock were allocated to subclasses based on hierarchical clustering of gene expression profiles, and we then compared clinical characteristics, plasma inflammatory markers, cell compositions using GEDIT, and immune repertoires using Imrep between the two subclasses. RESULTS: Patients with septic shock depicted alterations in innate and adaptive immune pathways. Among patients with septic shock, we identified two subtypes based on gene expression patterns. Compared with Subclass 2, Subclass 1 was characterized by upregulation of innate immunity pathways and downregulation of adaptive immunity pathways. Subclass 1 had significantly worse clinical outcomes despite the two classes having similar illness severity on initial clinical presentation. Subclass 1 had elevated levels of plasma inflammatory cytokines and endothelial injury biomarkers and demonstrated decreased percentages of CD4 T cells and B cells and less diverse T cell receptor repertoires. CONCLUSIONS: Two subclasses of pediatric septic shock patients were discovered through genome-wide expression profiling based on whole blood RNA sequencing with major biological and clinical differences. Trial Registration This is a secondary analysis of data generated as part of the observational CAF-PINT ancillary of the HALF-PINT study (NCT01565941). Registered March 29, 2012.

Purpose: The Joint Commission standards for titrated infusions require specification of maximum rates of infusion. This practice has led to the development of protocolized maximum doses that can be overridden by provider order ("soft maximums") and to dose caps that cannot be superseded ("hard maximums"). The purpose of this study was to determine the prevalence of and attitudes towards dose capping of norepinephrine. Methods: A 20-item cross-sectional survey assessing norepinephrine dose capping practices, perceptions of norepinephrine protocols, and respondent and practice site demographics was distributed electronically to the mailing list of an international medical podcast. Responses were stratified according to use of weight-based dosing (WBD) or non-WBD of norepinephrine. The primary objective was to characterize norepinephrine dosing practices including protocolized maximum doses and/or dose capping. Categorical and continuous variables were compared using the Chi-square test and Mann-Whitney U test, respectively, with P <.05 indicating statistical significance. Results: The survey was completed by 586 physicians, nurses, pharmacists, and advanced practice providers. WBD was used by 51% and non-WBD by 47%. A standardized titration protocol was reported by 65% and dose capping was reported by 19%. The protocolized maximum dose ranged from 20-400 mcg/min for respondents using non-WBD (median [interquartile range] 30 [30-50]) and ranged from.2-10 mcg/kg/min for respondents using WBD (1 [.5-3]). The dose cap was 50 (40-123) mcg/min with non-WBD and 2 (1-3) mcg/kg/min with WBD. Conclusions: An international, multi-professional survey of critical care and emergency medicine clinicians revealed wide variability in norepinephrine dosing practices including maximum doses allowed. [ABSTRACT FROM AUTHOR]

Purpose: Coroners' Prevention of Future Death (PFDs) reports are an under-utilized resource to learn about preventable deaths in England and Wales. We aimed to identify sepsis-related PFDs and explore the causes and concerns in this subset of preventable sepsis deaths. Methods: Four thousand three hundred five reports were acquired from the Courts and Tribunals Judiciary website between July 2013 and November 2022, which were screened for sepsis. Demographic information, coroners concerns and responses to these reports were extracted and analyzed, including a detailed paediatric subgroup analysis. Results: Two hundred sixty-five reports (6% of total PFDs) involved sepsis-related deaths. The most common cause of death in these reports was "sepsis without septic shock" (42%) and the most common site of infection was the respiratory system (18%) followed by gastrointestinal (16%) and skin (13%) infections. Specific pathogens were named in few reports (27%). Many deaths involved multimorbid patients (49%) or those with recent surgery (26%). Coroners named 773 individual concerns, the most frequent were: a failure to keep accurate records or notes (28%), failure in communication or handover (27%) or failure to recognize risk factors or comorbidities (20%). Paediatric cases frequently reported issues with sepsis screening tools (26%). Sepsis PFDs resulted in 421 individual reports being sent, of which 45% received no response. Most organisations who did respond acknowledged concerns and initiated a new change (74%). Conclusion: Sepsis-related PFDs provide valuable insights into preventable causes of sepsis and identify important sources of improvement in sepsis care. Wider dissemination of findings is vital to learn from these reports. [ABSTRACT FROM AUTHOR]

Background: Diagnosing sepsis remains a challenge because of the lack of gold-standard diagnostics. Since there are no simple, broadly accepted criteria for infection, there is a risk of misclassifying sepsis patients (sepsis mimics) among patients with organ failure. The main objective of this study was to investigate the proportion of non-infected patients (sepsis mimics) in ICU patients with presumed sepsis at intensive care unit (ICU) admission. Methods: Adult patients were screened retrospectively during 3.5 years in four ICUs in Sweden for fulfilment of the sepsis-3 criteria at ICU admission (presumed sepsis). Proxy criteria for suspected infection were sampled blood culture(s) and concomitant antibiotic administration. Culture-negative presumed sepsis patients were screened for infection according to the Linder-Mellhammar Criteria of Infection (LMCI). Sepsis mimics were defined as without probable infection according to the LMCI. Confirmed sepsis was defined as presumed sepsis after the exclusion of sepsis mimics. Results: In the ICU presumed sepsis cohort (2664 patients), 25% were considered sepsis mimics. The most common reasons for ICU admission among sepsis mimics were acute heart failure and unspecific respiratory failure. Comparing sepsis mimics and confirmed sepsis showed that confirmed sepsis patients were slightly more severely ill but had similar mortality. C-reactive protein had modest discriminatory power (AUROC 0.71) with confirmed sepsis as the outcome. Conclusions: One-fourth of a presumed ICU sepsis population identified with the sepsis-3 criteria could be considered sepsis mimics. The high proportion of sepsis mimics has a potential dilutional effect on the presumed sepsis population, which threatens the validity of results from sepsis studies using recommended sepsis criteria. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to determine the availability of neutrophilto-lymphocyte ratio (NLR) in diagnosis and treatment follow-up by determining the changing values when septic arthritis (SA) is diagnosed and during treatment. Material and Method: This retrospective study is based on examining the laboratory results of 44 adult patients with a diagnosis of SA. Laboratory values, white blood cell count (WBC), C-reactive protein (CRP), and NLR of the patients on days 0, 5, 10, and 14 and the results of the joint fluid analysis were evaluated Results: The mean number of cells in the joint fluid of the patients was 46 thousand, and the mean PMNL rate was 89.4%. Microorganisms were seen in gram staining of joint puncture fluid of only four patients (9.1%). The number of patients with growth in joint fluid culture was only 11 (25%). The mean values for days 0, 5, 10, and 14 were, respectively, 135.2, 88.1, 47.3, and 22.2 for CRP; 9.94, 7.86, 7.42, and 7.44 for WBC; 4.9, 3.8, 3.0 and 2.4 for NLR. Conclusion: NLR may serve as a valuable biomarker for diagnosing and monitoring treatment in SA, particularly given the low prevalence of microorganisms in gram stains and joint fluid cultures and the variability in cell counts in joint fluid samples. In patients diagnosed with SA, the mean NLR value is 4.9 and consistently decreases during treatment. Within two weeks of initiating treatment, NLR typically decreases by approximately half. This biomarker can aid in diagnosing and ongoing managing SA, offering a cost-effective and readily available indicator that should be routinely considered. [ABSTRACT FROM AUTHOR]

Objective To investigate the value of laboratory frailty index (FI-LAB) in predicting the risk of sepsis and septic shock in elderly hospitalized patients with community-acquired pneumonia (CAP). Methods A total of 502 elderly CAP patients hospitalized in Chengdu Fifth People's Hospital were retrospectively included. Forty routine laboratory indexes and vital signs collected for the first time within 24 hours after admission were selected to construct FI-LAB. Patients with FI-LAB ≥ 0.35 were defined as the frail group, while patients with FI-LAB＜ 0.35 were defined as the non-frail group. The occurrence of sepsis and septic shock was observed. The predictive model was established by modified Poisson regression, and the predictive value was analyzed by the ROC curve of the subjects. Results Multivariate modified Poisson regression analysis showed that frailty was a risk factor for sepsis (P＜0.001) and septic shock (P=0.001) in elderly patients with CAP (P＜0.001). When FI-LAB was multiplied by 100 and included in the multivariate Poisson regression analysis, it was found that for every 0.01 increase in FI-LAB, the risk of sepsis and septic shock increased by 5.9% and 6.2% (both P＜0.001). The area under ROC curve of FI-LAB for predicting sepsis and septic shock was 0.865 and 0.850 (both P＜0.001), respectively, and the best cut-off values were 0.28 and 0.42, respectively. Conclusion Frailty increases the risk of CAP complications with sepsis and septic shock. FI-LAB can predict the risk of sepsis in CAP patients and detect high-risk groups early. [ABSTRACT FROM AUTHOR]

This article discusses a case of progressive cervical swelling in a 6-year-old Belgian gelding. The horse presented with bilateral swelling of the caudal poll, and no history of trauma or injury was reported. Diagnostic imaging, including radiographs and ultrasound, revealed ovoid masses with mineral opaque foci and irregularities in the spinous process of the vertebrae. The findings were consistent with cranial nuchal bursitis and secondary osteitis. Bloodwork showed mild leukocytosis and positive titers for Lyme disease. Treatment involved aspiration of fluid from the masses and administration of minocycline and phenylbutazone. The horse showed improvement at the 2-week follow-up. [Extracted from the article]

Abstract Sepsis is a life-threatening state that arises due to a hyperactive inflammatory response stimulated by infection and rarely other insults (e.g., non-infections tissue injury). Although changes in several proinflammatory cytokines and signals are documented in humans and small animal models, far less is known about responses within affected tissues of large animal models. We sought to understand the changes that occur during the initial stages of inflammation by administering intravenous lipopolysaccharide (LPS) to Yorkshire pigs and assessing transcriptomic alterations in the brain, kidney, and whole blood. Robust transcriptional alterations were found in the brain, with upregulated responses enriched in inflammatory pathways and downregulated responses enriched in tight junction and blood vessel functions. Comparison of the inflammatory response in the pig brain to a similar mouse model demonstrated some overlapping changes but also numerous differences, including oppositely dysregulated genes between species. Substantial changes also occurred in the kidneys following LPS with several enriched upregulated pathways (cytokines, lipids, unfolded protein response, etc.) and downregulated gene sets (tube morphogenesis, glomerulus development, GTPase signal transduction, etc.). We also found significant dysregulation of genes in whole blood that fell into several gene ontology categories (cytokines, cell cycle, neutrophil degranulation, etc.). We observed a strong correlation between the brain and kidney responses, with significantly shared upregulated pathways (cytokine signaling, cell death, VEGFA pathways) and downregulated pathways (vasculature and RAC1 GTPases). In summary, we have identified a core set of shared genes and pathways in a pig model of systemic inflammation.

Abstract Background Reactive arthritis and septic arthritis rarely present concomitantly in the same joint and patient. Reactive arthritis presenting after coronavirus disease 2019 is also exceedingly rare, with less than 30 cases reported thus far. Less common pathogens such as Clostridium difficile have been reported to cause reactive arthritis, especially in patients with a positive human leukocyte antigen B27, and therefore should be considered in diagnostic algorithms. The aim of this case report is to highlight the difficulties and precautions in discerning and diagnosing patients presenting with sudden swelling of the knee. Case presentation We report the case of a 70-year-old Caucasian male with a recent history of coronavirus disease 2019 upper respiratory infection and diarrhea and negating trauma, who presented with a swollen and painful knee. Pain and swelling worsened and inflammatory parameters increased after an intraarticular corticosteroid injection. The patient was therefore treated with arthroscopic lavage and intravenous antibiotics for suspected septic arthritis. Synovial fluid and synovium samples were taken and sent for microbiological analysis. Synovial fluid cytology showed increased leukocytes at 10,980 × 106/L, while polymerase chain reaction and cultures came back sterile. Clostridium difficile toxin was later detected from a stool sample and the patient was treated with oral vancomycin. The patient was tested for the presence of human leukocyte antigen B27, which was positive. We present a review of the literature about the challenges of distinguishing septic from reactive arthritis, and about the mechanisms that predispose certain patients to this rheumatological disease. Conclusions It is still a challenge to differentiate between septic and reactive arthritis of the knee, and it is even more challenging to identify the exact cause of reactive arthritis. This case report of a human leukocyte antigen-B27-positive patient highlights the necessity of contemplating different, less common causes of a swollen knee joint as a differential diagnosis of an apparent septic infection, especially in the coronavirus disease 2019 era. Treating the patient for septic arthritis prevented any possible complications of such a condition, while treating the C. difficile infection contributed to the substantial relief of symptoms.

Background Septic shock, is associated with a high mortality rate and increased expenses. Currently, the first-line therapy for septic shock entails administering resuscitation fluids followed by infusing vasopressors when the blood pressure goal is not achieved. The recommended first-line vasopressor is norepinephrine, followed by vasopressin, epinephrine, angiotensin II, and dopamine. There is still a controversy on when each vasopressor should be administered. Therefore, we conducted this review to determine the impact and implications of vasopressor timing in septic shock patients. Methods PubMed, Medline, Cochrane Library, Web of Science, and Google Scholar databases were comprehensively searched for potential studies until October 2023. The methodological quality and bias assessment of valid records was examined with the Newcastle Ottawa Scale and Cochrane’s risk of bias tool. Additionally, all the meta-analyses were performed with Review Manager software. Results Twelve articles were eligible for review and analysis. Pooled analyses of data from 7 of these studies demonstrated lower incidence of mortality and shorter duration to achieve target mean arterial pressure in the early vs. late epinephrine groups (OR:0.44; 95%CI: 0.35–0.55; p Conclusion Early administration of norepinephrine has a mortality benefit and improves the duration taken to attain and sustain the goal MAP. Furthermore, early vasopressin possesses the potential to lower the fatality rate in individuals experiencing septic shock. However, further research is required to validate this finding.

In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.

IntroductionRecent studies have shown the prognostic value of capillary refill time (CRT) and suggested that resuscitation management guided by CRT may reduce morbidity and mortality in patients with septic shock. However, little is known about the current use of CRT in routine clinical practice. This study aimed to assess the modalities of CRT use among French adult and pediatric intensivists.MethodsA cross-sectional survey exploring CRT practices in acute circulatory failure was performed. The targeted population was French adult and pediatric intensivists (SFAR and GFRUP networks). An individual invitation letter including a survey of 32 questions was emailed twice. Descriptive and analytical statistics were performed.ResultsAmong the 6071 physicians who received the letter, 418 (7%) completed the survey. Among all respondents, 82% reported using CRT in routine clinical practice, mainly to diagnose acute circulatory failure, but 45% did not think CRT had any prognostic value. Perfusion goal-directed therapy based on CRT was viewed as likely to improve patient outcome by 37% of respondents. The measurement of CRT was not standardized as the use of a chronometer was rare (3%) and the average of multiple measurements rarely performed (46%). Compared to adult intensivists, pediatric intensivists used CRT more frequently (99% versus 76%) and were more confident in its diagnostic value and its ability to guide treatment.ConclusionCRT measurement is widely used by intensivists in patients with acute circulatory failure but most often in a non-standardized way. This may lead to a misunderstanding of CRT reliability and clinical usefulness.

Background: The aim of this study was to evaluate detection rates and risk factors for unsuspected proof of bacteria, as well as clinical and radiologic outcomes following femoral shaft nonunion without clinical signs of infection treated by a single-stage surgical revision procedure including reamed intramedullary exchange nailing. Methods: A retrospective cohort study was performed in a European level I trauma center between January 2015 and December 2022. Fifty-eight patients were included who underwent reamed intramedullary exchange nailing as a single-step procedure for surgical revision of posttraumatic diaphyseal femoral nonunion without any indications of infection in medical history and without clinical signs of local infection. Clinical details of the patients were analyzed and functional and radiologic long-term outcomes were determined. Results: In all patients, with and without proof of bacteria osseous, healing could be observed. The physical component summary of the SF-12 demonstrated significantly better results at least one year after the final surgical revision in case of a negative bacterial culture during exchange nailing. Conclusions: Clinical long-term outcomes demonstrated a trend towards better results following femoral shaft nonunion revision if there was no evidence for the presence of low-grade infected nonunion. In this case, a single-stage surgical procedure may be recommended. [ABSTRACT FROM AUTHOR]

Background and Objectives: The increase in the human population and the growth in water consumption on one hand, and the rise in sewage production on the other hand, have led to the expansion of environmental pollution threats. The objectives of the present study include launching a pilot project for the localization of knowledge in the design of artificial wetlands in accordance with the quantitative and qualitative conditions of domestic sewage in Iran (specifically, the dormitory of the University of Agricultural Sciences and Natural Resources in Sari) and investigating the possibility of replacing wetland systems with conventional domestic sewage treatment systems in the country. Materials and Methods: This study was conducted at the University of Agricultural Sciences and Natural Resources in Sari, involving the construction of six artificial wetlands, each with a length of 3 meters, width of 2 meters, and a height of 1.5 meters, using reinforced concrete. One of the ponds was excluded from the system due to leakage. Inside the ponds, artificial filters at different depths (1 meter: d1 and 1 meter and 30 centimeters: d2) and plant filters (Phragmites australis: p1 and Arundo donax: p2) were filled and planted. D10 and the coefficient of unifo rmity (CU) of the substrate materials were obtained as 2 millimeters and 3.625, respectively, from the grain size analysis. The hydraulic conductivity and porosity of the substrate were 2.523 cm/s and 39.2%, respectively. The specific surface area (SSA) of the substrate materials was calculated as 1.336 m²/kg (2245 m²/m³ of substrate materials). The effluent from the septic tank of the dormitory's baffled septic tank was injected onto the beds after a settling and dilution stage using a pump. In the initial loading, the beds were submerged below the surface, and a three-day retention time was allowed for the first sampling. Quality parameters of the wastewater, including biochemical oxygen demand (BOD), chemical oxygen demand (COD), total suspended solids (TSS), fecal coliform (FC), and total coliform (TC), were monitored to assess the performance of the treatment system. Results: Although the injected wastewater was diluted up to 25%, a significant removal efficiency of 51 to 55, 41 to 79, 74 to 89, 70 to 95.3, and 78 to 95 percent was achieved for BOD, COD, TSS, FC, and TC, respectively, in different treatments. Among the treatments, the weakest performance was associated with treatment P1D2, while the best purification performance was observed in treatment P2D1. This indicates the dominance of the physical characteristics of the systems at the beginning of the startup period on the purification performance. However, the initial performance of the treatment system was very promising and the removal of some parameters such as TSS and FC was at the average level of a full-fledged wetland treatment system. Conclusion: This wastewater treatment technology is recommended for all managers and experts in the country's wastewater industry, especially in rural areas with inexpensive land and a population of fewer than 5000 people. These conditions encompass all towns, universities, military barracks, and military facilities as well. [ABSTRACT FROM AUTHOR]

The United Nations has estimated that 2.8 billion individuals across the world will not have access to safely managed sanitation in 2030. In the accounting of global sanitation access, local inequities often are invisible to those counting, especially given that many of these counters are physically distant and often external to communities suffering from lack of access. Lowndes County, Alabama, a predominantly-Black county in rural Alabama (USA), provides a window into the social, racial, and environmental injustices that are present in the rural American South. Our survey of household sanitation access in Lowndes County, implemented by a collaboration of an academic institution, a local environmental justice organisation, and residents, shows that community members in the county are aware of the problems associated with failing septic systems. Producing data that can make publicly visible the lack of access to sanitation will, however, remain a challenge until institutional and structural barriers are overcome. [ABSTRACT FROM AUTHOR]

Background: Reactive arthritis and septic arthritis rarely present concomitantly in the same joint and patient. Reactive arthritis presenting after coronavirus disease 2019 is also exceedingly rare, with less than 30 cases reported thus far. Less common pathogens such as Clostridium difficile have been reported to cause reactive arthritis, especially in patients with a positive human leukocyte antigen B27, and therefore should be considered in diagnostic algorithms. The aim of this case report is to highlight the difficulties and precautions in discerning and diagnosing patients presenting with sudden swelling of the knee. Case presentation: We report the case of a 70-year-old Caucasian male with a recent history of coronavirus disease 2019 upper respiratory infection and diarrhea and negating trauma, who presented with a swollen and painful knee. Pain and swelling worsened and inflammatory parameters increased after an intraarticular corticosteroid injection. The patient was therefore treated with arthroscopic lavage and intravenous antibiotics for suspected septic arthritis. Synovial fluid and synovium samples were taken and sent for microbiological analysis. Synovial fluid cytology showed increased leukocytes at 10,980 × 106/L, while polymerase chain reaction and cultures came back sterile. Clostridium difficile toxin was later detected from a stool sample and the patient was treated with oral vancomycin. The patient was tested for the presence of human leukocyte antigen B27, which was positive. We present a review of the literature about the challenges of distinguishing septic from reactive arthritis, and about the mechanisms that predispose certain patients to this rheumatological disease. Conclusions: It is still a challenge to differentiate between septic and reactive arthritis of the knee, and it is even more challenging to identify the exact cause of reactive arthritis. This case report of a human leukocyte antigen-B27-positive patient highlights the necessity of contemplating different, less common causes of a swollen knee joint as a differential diagnosis of an apparent septic infection, especially in the coronavirus disease 2019 era. Treating the patient for septic arthritis prevented any possible complications of such a condition, while treating the C. difficile infection contributed to the substantial relief of symptoms. [ABSTRACT FROM AUTHOR]

Sepsis is a life-threatening state that arises due to a hyperactive inflammatory response stimulated by infection and rarely other insults (e.g., non-infections tissue injury). Although changes in several proinflammatory cytokines and signals are documented in humans and small animal models, far less is known about responses within affected tissues of large animal models. We sought to understand the changes that occur during the initial stages of inflammation by administering intravenous lipopolysaccharide (LPS) to Yorkshire pigs and assessing transcriptomic alterations in the brain, kidney, and whole blood. Robust transcriptional alterations were found in the brain, with upregulated responses enriched in inflammatory pathways and downregulated responses enriched in tight junction and blood vessel functions. Comparison of the inflammatory response in the pig brain to a similar mouse model demonstrated some overlapping changes but also numerous differences, including oppositely dysregulated genes between species. Substantial changes also occurred in the kidneys following LPS with several enriched upregulated pathways (cytokines, lipids, unfolded protein response, etc.) and downregulated gene sets (tube morphogenesis, glomerulus development, GTPase signal transduction, etc.). We also found significant dysregulation of genes in whole blood that fell into several gene ontology categories (cytokines, cell cycle, neutrophil degranulation, etc.). We observed a strong correlation between the brain and kidney responses, with significantly shared upregulated pathways (cytokine signaling, cell death, VEGFA pathways) and downregulated pathways (vasculature and RAC1 GTPases). In summary, we have identified a core set of shared genes and pathways in a pig model of systemic inflammation. Highlights: Robust inflammatory response in pig brain following LPS, with significant differences from a similar mouse model. Shared genes and pathways in the brain and kidneys following LPS in a pig model. Characterization of gene-level and isoform-level transcriptional alterations in blood, brain, and kidney post-LPS challenge in a pig model. [ABSTRACT FROM AUTHOR]

Background: COVID-19 was associated with an increased number of patients with mucormycosis (MCR), followed by septic cavernous sinus thrombosis (SCST). We evaluated the association between anticoagulation (AC) and mortality/morbidity of COVID-19-associated MCR (CAM)-induced SCST. Methods: In this retrospective study, neurological sequelae, functional outcomes, and in-hospital mortality were compared between AC receivers and non-receivers. In addition, the association between AC and survivability was examined. Results: Twenty-nine patients (17 male; mean age: 51.27 years) with CAM-induced SCST were included in the study. The median intervals between COVID-19 and MCR, and COVID-19 and SCST were 19 and 27 days, respectively. [ABSTRACT FROM AUTHOR]

Background: Buffered crystalloid solutions are often recommended as the first choice for intravenous resuscitation. Sepsis-related morbidity and mortality are lower when patients with septic shock are resuscitated early. Purpose: To compare the efficacy and potency of lactate clearance, resolution of metabolic acidosis, improvement in hemodynamic status, and resolution of shock after resuscitation with lactate- and acetatebuffered solutions in septic shock. Methods: Of the 60 patients with septic shock and sepsis, 30 were recruited for lactate solution and 30 for acetate solution. After admission of these patients to the ICU, we perform ABG of the patient to determine baseline PH, PCO2, PO2, bicarbonate, and lactate. After 12 hours of resuscitation, we repeat the ABG to determine the improvement in sepsis/septic lactate clearance and resolution of metabolic acidosis in both groups. Results:The mean change in pH and pO2 was significantly increased and pCO2 significantly decreased in the acetate group from admission to 12 hours after admission, whereas only pO2 was significantly increased in the lactate group. Mean lactate values at admission and after 12 hours were 6.20±2.67 and 4.60±2.13, respectively, in the acetate group and 5.24±1.44 and 2.98±0.53, respectively, in the lactate group. Mean SBP (mmHg) and DBP (mmHg) were significantly increased, and HR (beats/min) and RR (/min) were significantly decreased from admission to 12 hours after admission in the acetate group and the lactate group. Conclusion: Mean lactate was significantly decreased more in the lactate group (2.26) than in the acetate group. In addition, SBP (mmHg) and DBP (mmHg) were increased more and HR (beats/min) decreased more in the acetate group than in the lactate group. [ABSTRACT FROM AUTHOR]

Abstract Background The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. Methods Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. Results Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2–161.5], p = 0.0028). Similarly, oxygenation index decreased by − 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus − 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI − 8.6 to − 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5–47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. Conclusions In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. Trial Registration: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015).

Abstract As an emerging surgical technology, tissue removal systems have been widely used in the treatment of endometrial polyps due to its characteristics of less endometrial damage, shorter learning curve and clearer vision of the operative field. There are few cases in the literature reporting serious complications after endometrial polypectomy using tissue removal systems. As known, septic shock is a rare complication following hysteroscopic polypectomy. Now, we present the case of a 23-year-old woman who developed septic shock after polypectomy with tissue removal system. The patient had a history of recurrent vaginitis for more than half a year. Due to endometrial polyps, she was admitted to our hospital and scheduled to undergo hysteroscopic endometrial polypectomy. Three hours after the endometrial polypectomy using the tissue removal system, the patient had shock symptoms such as increased body temperature, decreased blood pressure and increased heart rate. Then, the patient was successfully treated and discharged after anti-infection and anti-shock treatments. The purpose of this case report is to remind clinicians to consider the possibility of serious infection and comprehensively evaluate the risk of infection before choosing hysteroscopic devices for endometrial polyps, especially for patients who choose the mechanical hysteroscopic tissue removal systems. Furthermore, the mechanical hysteroscopic tissue removal systems should be used with caution in patients with previous recurrent vaginitis.

Background: The physiological effects of renin-angiotensin system modulation in acute respiratory distress syndrome (ARDS) remain controversial and have not been investigated in randomized trials. We sought to determine whether angiotensin-II treatment is associated with improved oxygenation in shock-associated ARDS. Methods: Post-hoc subgroup analysis of the Angiotensin Therapy for High Output Shock (ATHOS-3) trial. We studied patients who met modified Berlin ARDS criteria at enrollment. The primary outcome was PaO2/FiO2-ratio (P:F) at 48-h adjusted for baseline P:F. Secondary outcomes included oxygenation index, ventilatory ratio, PEEP, minute-ventilation, hemodynamic measures, patients alive and ventilator-free by day-7, and mortality. Results: Of 81 ARDS patients, 34 (42%) and 47 (58%) were randomized to angiotensin-II or placebo, respectively. In angiotensin-II patients, mean P:F increased from 155 mmHg (SD: 69) at baseline to 265 mmHg (SD: 160) at hour-48 compared with no change with placebo (148 mmHg (SD: 63) at baseline versus 164 mmHg (SD: 74) at hour-48)(baseline-adjusted difference: + 98.4 mmHg [95%CI 35.2–161.5], p = 0.0028). Similarly, oxygenation index decreased by − 6.0 cmH2O/mmHg at hour-48 with angiotensin-II versus − 0.4 cmH2O/mmHg with placebo (baseline-adjusted difference: -4.8 cmH2O/mmHg, [95%CI − 8.6 to − 1.1], p = 0.0273). There was no difference in PEEP, minute ventilation, or ventilatory ratio. Twenty-two (64.7%) angiotensin-II patients had sustained hemodynamic response to treatment at hour-3 versus 17 (36.2%) placebo patients (absolute risk-difference: 28.5% [95%CI 6.5–47.0%], p = 0.0120). At day-7, 7/34 (20.6%) angiotensin-II patients were alive and ventilator-free versus 5/47(10.6%) placebo patients. Day-28 mortality was 55.9% in the angiotensin-II group versus 68.1% in the placebo group. Conclusions: In post-hoc analysis of the ATHOS-3 trial, angiotensin-II was associated with improved oxygenation versus placebo among patients with ARDS and catecholamine-refractory vasodilatory shock. These findings provide a physiologic rationale for trials of angiotensin-II as treatment for ARDS with vasodilatory shock. Trial Registration: ClinicalTrials.Gov Identifier: NCT02338843 (Registered January 14th 2015). [ABSTRACT FROM AUTHOR]

Purpose: The dose and timing of early fluid resuscitation in sepsis remains a debated topic. The objective of this study is to evaluate the effect of fluid timing in early sepsis management on mortality and other clinical outcomes. Methods: Single-center, retrospective cohort study of emergency-department-treated adults (>18 years, n = 1032) presenting with severe sepsis or septic shock. Logistic regression evaluating the impact of 30 mL/kg crystalloids timing and mortality-versus-time plot controlling for mortality in emergency department sepsis score, lactate, antibiotic timing, obesity, sex, systemic inflammatory response syndrome criteria, hypotension, and heart and renal failures. This study is a subanalysis of a previously published investigation. Results: Mortality was 17.1% (n = 176) overall and 20.4% (n = 133 of 653) among those in septic shock. 30 mL/kg was given to 16.9%, 32.2%, 16.2%, 14.5%, and 20.3% of patients within ≤1, 1 ≤ 3, 3 ≤ 6, 6 ≤ 24, and not reached within 24 h, respectively. A 24-h plot of adjusted mortality versus time did not reach significance, but within the first 12 h, the linear function showed a per-hour mortality increase (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.02-1.67) which peaks around 5h, although the quadratic function does not reach significance (P =.09). When compared to patients receiving 30 mL/kg within 1 h, increased mortality was observed when not reached within 24 h (OR 2.69, 95% CI 1.37-5.37) but no difference when receiving this volume between 1 and 3 (OR 1.11, 95% CI 0.62-2.01), 3 and 6 (OR 1.83, 95% CI 0.97-3.52), or 6 and 24 h (OR 1.51, 95% CI 0.75-3.06). Receiving 30 mL/kg between 1 and 3 versus <1 h increased the incidence of delayed hypotension (OR 1.83, 95% CI 1.23-2.72) but did not impact need for intubation, intensive care unit admission, or vasopressors. Conclusions: We observed weak evidence that supports that earlier is better for survival when reaching fluid goals of 30 mL/kg, but benefits may wane at later time points. These findings should be viewed as hypothesis generating. [ABSTRACT FROM AUTHOR]

As an emerging surgical technology, tissue removal systems have been widely used in the treatment of endometrial polyps due to its characteristics of less endometrial damage, shorter learning curve and clearer vision of the operative field. There are few cases in the literature reporting serious complications after endometrial polypectomy using tissue removal systems. As known, septic shock is a rare complication following hysteroscopic polypectomy. Now, we present the case of a 23-year-old woman who developed septic shock after polypectomy with tissue removal system. The patient had a history of recurrent vaginitis for more than half a year. Due to endometrial polyps, she was admitted to our hospital and scheduled to undergo hysteroscopic endometrial polypectomy. Three hours after the endometrial polypectomy using the tissue removal system, the patient had shock symptoms such as increased body temperature, decreased blood pressure and increased heart rate. Then, the patient was successfully treated and discharged after anti-infection and anti-shock treatments. The purpose of this case report is to remind clinicians to consider the possibility of serious infection and comprehensively evaluate the risk of infection before choosing hysteroscopic devices for endometrial polyps, especially for patients who choose the mechanical hysteroscopic tissue removal systems. Furthermore, the mechanical hysteroscopic tissue removal systems should be used with caution in patients with previous recurrent vaginitis. [ABSTRACT FROM AUTHOR]

Background: An important contributor to mortality and morbidity in intensive care unit [ICU] is sepsis. Increased mortality has been linked to putting off diagnosis and beginning the right treatment.Aim of the Study: In this investigation, the effectiveness of serum procalcitonin as a biomarker for septic critically unwell patients' antibiotic medication duration was be assessed.Patients and Methods: In this research, 50 individuals who met the inclusion criteria and required antibiotic therapy due to confirmed or strongly suspected bacterial infections were randomly divided into two groups, each of which had 25 patients. The other 25 patients received antibiotics in accordance with our ICU protocol [Group C-control group], while 25 patients received antibiotics in accordance with serum procalcitonin [PCT] guidance [Group P-PCT guided group].Results: PCT guidance enables a decrease in the dosage of antibiotics given to critically ill individuals with severe sepsis & septic shock. It was noticeable that the PCT group had much shorter periods of antibiotic therapy [mean of 4 days of less exposure to antibiotics and about 6 days shorter lengths of ICU stay]. The PCT group also had significantly fewer days spent in the hospital overall.Conclusion: An algorithm utilizing serial procalcitonin [PCT] measurements has been found to enable a more prudent utilization of antibiotics in individuals diagnosed with severe sepsis and septic shock. This approach effectively and safely reduces the duration of antibiotic exposure, as well as the length of ICU and hospital stays.

Background/aimsDespite evidence that preferential use of balanced/buffered fluids may improve outcomes compared with chloride-rich 0.9% saline, saline remains the most commonly used fluid for children with septic shock. We aim to determine if resuscitation with balanced/buffered fluids as part of usual care will improve outcomes, in part through reduced kidney injury and without an increase in adverse effects, compared to 0.9% saline for children with septic shock.MethodsThe Pragmatic Pediatric Trial of Balanced versus Normal Saline Fluid in Sepsis (PRoMPT BOLUS) study is an international, open-label pragmatic interventional trial being conducted at > 40 sites in the USA, Canada, and Australia/New Zealand starting on August 25, 2020, and continuing for 5 years. Children > 6 months to

BackgroundReduced cholesterol levels are associated with increased organ failure and mortality in sepsis. Cholesterol levels may vary by infection type (gram negative vs positive), possibly reflecting differences in cholesterol-mediated bacterial clearance.MethodsThis was a secondary analysis of a combined data set of 2 prospective cohort studies of adult patients meeting Sepsis-3 criteria. Infection types were classified as gram negative, gram positive, or culture negative. We investigated quantitative (levels) and qualitative (dysfunctional high-density lipoprotein [HDL]) cholesterol differences. We used multivariable logistic regression to control for disease severity.ResultsAmong 171 patients with sepsis, infections were gram negative in 67, gram positive in 46, and culture negative in 47. Both gram-negative and gram-positive infections occurred in 11 patients. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and HDL cholesterol (HDL-C) levels were lower for culture-positive sepsis at enrollment (TC, P < .001; LDL-C, P < .001; HDL-C, P = .011) and persisted after controlling for disease severity. Similarly, cholesterol levels were lower among culture-positive patients at 48 hours (TC, P = .012; LDL-C, P = .029; HDL-C, P = .002). Triglyceride (TG) levels were lower at enrollment (P =.033) but not at 48 hours (P = .212). There were no differences in dysfunctional HDL. Among bacteremic patients, cholesterol levels were lower at enrollment (TC, P = .010; LDL-C, P = .010; HDL-C, P ≤ .001; TG, P = .005) and at 48 hours (LDL-C, P = .027; HDL-C, P < .001; TG, P = .020), except for 48 hour TC (P = .051). In the bacteremia subgroup, enrollment TC and LDL-C were lower for gram-negative versus gram-positive infections (TC, P = .039; LDL-C, P = .023).ConclusionCholesterol levels are significantly lower among patients with culture-positive sepsis and bacteremia.

Background: Sepsis is a complex, life-threatening clinical syndrome that can cause other related diseases, such as acute kidney injury (AKI). Circular RNA (circRNA) is a type of non-coding RNA with a diverse range of functions, and it plays essential roles in miRNA sponge. CircRNA plays a huge part in the development of various diseases. CircRNA and the competing endogenous RNA (ceRNA) regulatory network are unknown factors in the onset and progression of septic AKI (SAKI). This study aimed to clarify the complex circRNA-associated regulatory mechanism of circRNAs in SAKI. Methods: We collected 40 samples of whole blood of adults, including 20 cases of SAKI and 20 cases of healthy controls. Moreover, five cases were each analyzed by RNA sequencing, and we identified differentially expressed circRNA, miRNA, and mRNA (DEcircRNAs, DEmiRNAs, and DEmRNAs, respectively). All samples were from SAKI patients with intraperitoneal infection. Results: As a result, we screened out 236 DEcircRNAs, 105 DEmiRNAs, and 4065 DEmRNAs. Then, we constructed two co-expression networks based on RNA–RNA interaction, including circRNA–miRNA and miRNA–mRNA coexpression networks. We finally created a circRNA–miRNA–mRNA regulation network by combining the two co-expression networks. Functional and pathway analyses indicated that DEmRNAs in ceRNA were mostly concentrated in T cell activation, neutrophils and their responses, and cytokines. The protein–protein interaction network was established to screen out the key genes participating in the regulatory network of SAKI. The hub genes identified as the top 10 nodes included the following: ZNF727, MDFIC, IFITM2, FOXD4L6, CIITA, KCNE1B, BAGE2, PPIAL4A, USP17L7, and PRSS2. Conclusion: To our knowledge, this research is the first study to describe changes in the expression profiles of circRNAs, miRNAs, and mRNAs in patients with SAKI. These findings provide a new treatment target for SAKI treatment and novel ideas for its pathogenesis. [ABSTRACT FROM AUTHOR]

Objective: Rare coexistence of disease or pathology Background: Infectious diarrheal illnesses such as rotavirus gastroenteritis are significant contributors to childhood morbidity and mortality, especially in low socio-demographic index regions. Major advances in addressing this issue include sanitation and clean water initiatives, as well as rotavirus immunization. In Australia, a robust vaccination program has significantly reduced childhood rotavirus infections, leading to decreased hospitalizations and mortality. However, cases of adult rotavirus still occur, and although these adult patients usually do not require interventional management, it is possible for them to present critically unwell and require resuscitation. Case Report: A previously well 65-year-old man presented to the Emergency Department febrile and hypotensive with severe diarrhea attributed to rotavirus. Clinically, he presented with mixed hypovolemic and septic shock. Despite initial resuscitation, he had multiple severe acute end-organ complications, secondary to poor perfusion. He acquired an acute kidney injury, type-2 myocardial infarction, and ischemic hepatic injury. The mainstay of management was rapid fluid resuscitation, continuous renal replacement therapy, and monitoring in the Intensive Care Unit; however, it was crucial to empirically treat for other causes of shock. Conclusions: To the best of our knowledge, there is a scarcity of reports documenting the management of severe rotavirus gastroenteritis in adults. We recommend advising elderly patients to avoid contact with individuals with diarrheal illnesses, especially rotavirus gastroenteritis. Clinicians should also promote awareness regarding the potential severity of a disease that is typically managed conservatively, and be aware that intervention can be required in severe gastroenteritis. [ABSTRACT FROM AUTHOR]

Summary: Equine septic fungal arthritis is poorly documented in the literature. There is an absence of efficacy and safety data for antifungal medications, highlighting the importance of documenting this case. A 15‐year‐old Irish sport horse gelding presented 4/5 (AAEP) left hindlimb lame 13 days after intra‐articular medication of the left tarsocrural joint with triamcinolone and hyaluronic acid. Radiography revealed an osteochondral fragment at the distal intermediate ridge of the tibia and shallow subchondral bone defect on the medial trochlear ridge. Synoviocentesis yielded a turbid sample with an elevated total nucleated cell count (49 × 109cells/L; total neutrophil count of 62.8%). Arthroscopic lavage of the tarsocrural joint (TCJ) was performed. Ceftriaxone was administered and systemic antimicrobials initiated. The fungus Wickerhamomyces anomalus was identified on culture. The horse was subsequently intensively treated with antimicrobial and antifungal medications, both systemically and intra‐articularly over the following 60 plus days. Multiple subsequent synovial cultures revealed the persistence of the fungal organism, until a negative culture on day 55. However, on day 113, a grade 5/5 lameness was present, and a further positive synovial fungal culture. Radiographs revealed a lytic lesion at the distal tibia with marked progression. The horse was euthanised on day 126. [ABSTRACT FROM AUTHOR]

The results from a four-year study of a freshwater pond on Long Island, NY, USA, do not point to a single source of boron (and by proxy other elements including nutrients) in this system. However, boron data from samples associated with this pond can be explained by mixing between average precipitation (weighted average δ11B = 22.7) in the area and the local sources of boron, both natural and anthropogenic. This multiyear study provided the opportunity to see both yearly and seasonal differences. One algae sample from the pond showed significant fractionation and enrichment in light boron relative to the water and suggests algae may act as a boron sink. This type of biological fractionation could explain an observed down-gradient trend to heavier boron isotope values in pond water, which corresponds to the slight reduction in boron concentration seen in 2021. However, the trend was subdued in the following year, likely due to differences in the water flow rates and/or rate of algal growth. An opposite trend was seen with depth in the water, where δ11B showed a positive correlation to boron concentration, which increased with depth from the surface of the pond. This gradient may be explained by the stratification of the pond with a heavy source concentrating in the bottom waters. The bottom water composition was consistent with goose feces (δ11B = 25.8) or the addition of chemicals from the application of rock salt to local roads in winter. Surprisingly, boron from seawater (average δ11B = 39.8) did not appear to have a direct impact on Setauket Pond, other than its influence on precipitation, providing heavy δ11B and very low boron concentrations. [ABSTRACT FROM AUTHOR]

Background: Sepsis is known as a life-threatening organ dysfunction that is caused by a dysregulated host response to infection. Sepsis and septic shock carries high potential mortality rates, resulting in challenge and burden to healthcare system. Variation in the size of red blood cells is represented by RED cell distribution width. It is thought to be elevated when an excess amount of reticulocytes are released into circulation. RDW parameter is provided in the CBC report done by the automated analyzer. It is an inexpensive, routinely available, and rapidly measurable prognostic tool. Methodology- The study was carried out at the ICCU, Department of Medicine of tertiary care center, for period of 15-18 months. 65 patients fulfilling the inclusion and exclusion criteria were considered for the study. RDW value was recorded and it correlation with APACHE II score and mortality among the patients was noted. Data was entered in MS EXCEL spread sheet and analysed with the help of Open epi and spss software. Results- Mean age group of study population among non-survivor patient was 48.64 with SD of 17.26 and of survivor was 39.91 with SD of 16.64. Mean APACHE II score among Group I was 16.333 with SD of 7.711, in Group II was 21.307 with SD of 8.596 and in Group III was 21 with SD of 8.5. 30 days mortality among Group I was 1 (16%) in Group II was 22 (84.62%) and in Group III was 30 (90.91%). Conclusion- RDW value increased in patients with sepsis. [ABSTRACT FROM AUTHOR]

Elderly patients are frequently presenting with emergency surgical conditions. The open abdomen technique is widely used in abdominal emergencies needing rapid control of intrabdominal contamination. However, specific predictors of mortality identifying candidates for comfort care are understudied. The 2013-2017 the American College of Surgeons-National Surgical Quality Improvement Program database was queried for emergent laparotomies performed in geriatric patients with sepsis or septic shock in whom fascial closure was delayed. Patients with acute mesenteric ischemia were excluded. The primary outcome was 30-d mortality. Univariable analysis, followed by multivariable logistic regression, was performed. Mortality was computed for combinations of the five predictors with the highest odds ratios (OR). A total of 1399 patients were identified. The median age was 73 (69-79) y, and 54.7% were female. 30-d mortality was 50.6%. In the multivariable analysis, the most important predictors were as follows: American Society of Anesthesiologists status 5 (OR = 4.80, 95% confidence interval [CI], 1.85-12.49 P = 0.002), dialysis dependence (OR = 2.65, 95% CI 1.54-4.57, P < 0.001), congestive hearth failure (OR = 2.53, 95% CI 1.52-4.21, P < 0.001), disseminated cancer (OR = 2.61, 95% CI 1.55-4.38, P < 0.001), and preoperative platelet count of <100,000 cells/μL (OR = 1.87, 95% CI 1.15-3.04, P = 0.011). The presence of two or more of these factors resulted in over 80% mortality. The absence of all these risk factors results in a survival rate of 62.1%. In elderly patients, surgical sepsis or septic shock requiring an open abdomen for surgical management is highly lethal. The presence of several combinations of preoperative comorbidities is associated with a poor prognosis and can identify patients who can benefit from timely initiation of palliative care. [ABSTRACT FROM AUTHOR]

Circulatory shock is a common condition that carries high morbidity and mortality. This review aims to update the critical steps in managing common types of shock in adult patients admitted to medical emergency and intensive care units. A literature review was performed by searching PubMed, EMBASE Ovid, and Cochrane Library, using the following search items: ("shock" OR "circulatory shock" OR "septic shock" OR "cardiogenic shock") AND ("management" OR "treatment" OR "resuscitation"). The review emphasizes prompt shock identification with tissue hypoperfusion, knowledge of the underlying pathophysiological mechanism, initial fluid resuscitation with balanced crystalloids, norepinephrine as the preferred vasopressor in septic and profound cardiogenic shock, and tailored intervention addressing specific etiologies. Point-of-care ultrasound may help evaluate an undifferentiated shock and determine fluid responsiveness. The approach to septic shock is improving; however, confirmatory studies are required for many existing (e.g., amount of initial fluids and steroids) and emerging (e.g., angiotensin II) therapies. Knowledge gaps and wide variations persist in managing cardiogenic shock that needs urgent addressing to improve outcomes. [ABSTRACT FROM AUTHOR]

Background: Acute hand infections are a common occurrence in the South African healthcare setting, often requiring specialist care. This study aimed to describe the incidence of acute hand infections requiring surgery before and after the introduction of COVID-19 hand hygiene guidelines. Methods: A retrospective cohort study compared acute hand infections at Worcester Provincial Hospital (WPH) during two periods in 2020, before (period 1) and after (period 2) the COVID-19 regulations were implemented. A control, which consisted of data from the same periods in the years 2018 and 2019 was used to compare findings. Results: A total of 279 acute hand infections were identified for the three years, of which 2020 had the most cases (100 infections). In 2020, the total number of infections decreased by 56% from period 1 (64 infections) to period 2 (36 infections). However, the incidence increased from 12.4% (period 1) to 15% (period 2). Conclusion: Although the total number of acute hand infections decreased significantly, the incidence increased. These findings occurred during two periods, before and after strict hand hygiene regulations were implemented. The findings of this study could not decisively support that increased hand hygiene had any effect on the incidence of acute hand infections. [ABSTRACT FROM AUTHOR]