Comparative pharmacokinetic study of Anisodamine Hydrobromide tablets and injection in septic acute lung injury rats.

Aim: We aimed to establish a sensitive LC-MS/MS method to analyze the pharmacokinetics of Ani HBr tablets and injection. Methods: Around 10 mmNH4Ac containing 0.1% formic acid and acetonitrile were used as the mobile phase. Acute lung injury in septic and normal rats, respectively, were administered Ani HBr tablets at doses of 12.5, 25 and 50 mg/kg and injection at doses of 4, 8 and 16 mg/kg, followed by extraction of the drugs from plasma using ethyl acetate for subsequent analysis. Results & conclusion: The method met the requirements for biological analysis. Ani HBr tablets absorbed slowly in rats with disease, tail vein administration was a more promising approach for treating septic acute lung injury.

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Key summary of German national guideline for adult patients with nosocomial pneumonia- Update 2024 Funding number at the Federal Joint Committee (G-BA): 01VSF22007.

PURPOSE: This executive summary of a German national guideline aims to provide the most relevant evidence-based recommendations on the diagnosis and treatment of nosocomial pneumonia. METHODS: The guideline made use of a systematic assessment and decision process using evidence to decision framework (GRADE). Recommendations were consented by an interdisciplinary panel. Evidence analysis and interpretation was supported by the German innovation fund providing extensive literature searches and (meta-) analyses by an independent methodologist. For this executive summary, selected key recommendations are presented including the quality of evidence and rationale for the level of recommendation. RESULTS: The original guideline contains 26 recommendations for the diagnosis and treatment of adults with nosocomial pneumonia, thirteen of which are based on systematic review and/or meta-analysis, while the other 13 represent consensus expert opinion. For this key summary, we present 11 most relevant for everyday clinical practice key recommendations with evidence overview and rationale, of which two are expert consensus and 9 evidence-based (4 strong, 5 weak and 2 open recommendations). For the management of nosocomial pneumonia patients should be divided in those with and without risk factors for multidrug-resistant pathogens and/or Pseudomonas aeruginosa. Bacterial multiplex-polymerase chain reaction (PCR) should not be used routinely. Bronchoscopic diagnosis is not considered superior to´non-bronchoscopic sampling in terms of main outcomes. Only patients with septic shock and the presence of an additional risk factor for multidrug-resistant pathogens (MDRP) should receive empiric combination therapy. In clinically stabilized patients, antibiotic therapy should be de-escalated and focused. In critically ill patients, prolonged application of suitable beta-lactam antibiotics should be preferred. Therapy duration is suggested for 7-8 days. Procalcitonin (PCT) based algorithm might be used to shorten the duration of antibiotic treatment. Patients on the intensive care unit (ICU) are at risk for invasive pulmonary aspergillosis (IPA). Diagnostics for Aspergillus should be performed with an antigen test from bronchial lavage fluid. CONCLUSION: The current guideline focuses on German epidemiology and standards of care. It should be a guide for the current treatment and management of nosocomial pneumonia in Germany.

Mitral Valve Repair in a 15-Month-Old Child With Kingella kingae Endocarditis.

Kingella kingae, a Haemophilus parainfluenzae, Aggregatibacter actinomycetemcomitans, Aggregatibacter aphrophilus, Cardiobacterium hominis, Eikenella corrodens, K. kingae (HACEK) organism, is commonly found in the oropharynx. Although it rarely causes endocarditis, it can pose a significant risk to young children. We report a case of K. kingae endocarditis in a previously healthy 15-month-old male who initially presented with symptoms of an upper respiratory infection. Blood cultures taken at 60 hours revealed the presence of K. kingae. Subsequent echocardiogram and brain MRI demonstrated large vegetation on the mitral valve and septic emboli in the right occipital and left posterior parietal lobes. The patient was treated with intravenous ceftriaxone and underwent mitral valve repair with annuloplasty. This case illustrates the presentation of K. kingae endocarditis with initial respiratory symptoms and the subsequent identification of the infection through blood cultures and imaging. For pediatric patients presenting with upper respiratory symptoms, there may be clinical benefit to noninvasive ultrasound imaging to help rule out atypical pathologies like endocarditis.

Performance evaluation of modified Living Wall garden for treating septic tank effluent.

The Living Wall (LW) garden system has been employed as a post-treatment system to improve the effluent quality of septic tanks. This improvement primarily involves reducing nutrient levels, as well as facilitating the removal of organic matter and solids in accordance with effluent discharge guidelines. The objective of this study was to investigate the treatment performance of the LW system connected to a septic tank, along with an examination of the microbial communities within the LW units. A laboratory-scale LW system, comprising LW1, LW2, and LW3 units, was employed. The system was fed with effluent obtained from septic tanks and varied by theoretical hydraulic retention time (HRT) of 6, 12, and 24 h. The TCOD, SCOD, TSS, TVS, TKN, and TP removal efficiencies of the LWs were achieved at 62 ± 24, 42 ± 19, 72 ± 21, 66 ± 15, 80 ± 15, and 58 ± 21%, respectively. To classify microbial communities in the soil and gravels collected from each LW unit, the Illumina MiSeq System Sequencer was employed. Nitrospirota was consistently found in all LW units, aiding in the conversion of nitrogen. Fusobacteriota were detected in specific layers of the LW units, indicating varying oxygen levels in the LW system.

Arthroscopic treatment of septic arthritis of the ankle joint caused by streptococcus in patients with chronic inflammatory diseases: two case reports.

This report describes the arthroscopic treatment of septic arthritis of the ankle joint in two patients with inflammatory diseases, including rheumatoid arthritis (RA) and nail psoriasis. We treated both the ankle joints with antibiotic administration and urgent arthroscopic synovectomy and irrigation, although the procedure was performed several days (4 and 6 days) after the time at which the infection would have occurred. Fortunately, no recurrence has been seen for more than 18 and 20 months, respectively, after surgery, without antibiotic administration. Although septic arthritis of the ankle joint accounts for a small proportion of joint arthritis cases, diagnosis as early as possible is important. Our experience suggests that arthroscopic synovectomy and irrigation are effective for septic ankle arthritis even in chronic inflammatory disease cases.

Isolated Acromioclavicular Joint Septic Arthritis: A Case Report and Review of Literature.

A 60-year-old diabetic patient presented with acute pain and swelling localized to the left acromioclavicular joint. Laboratory and radiological investigations revealed the presence of pus in the left acromioclavicular joint along with bony erosion of the lateral end of the left clavicle. She was treated with open arthrotomy, debridement, and appropriate antibiotics for the causative methicillin-resistant Staphylococcus aureus (MRSA) infection. Prompt diagnosis and timely intervention can reduce the morbidity and mortality due to septic arthritis. We conducted a review of the literature on patients treated for isolated septic arthritis of the acromioclavicular joint.

Emphysematous Osteomyelitis of the Lumbar Spine and Sacrum After Liver Transplantation: A Case Report.

Emphysematous osteomyelitis (EO) is a rare and potentially fatal disease that often occurs in patients with underlying conditions, most commonly diabetes mellitus. Herein, we report a case of a 62-year-old man who presented with fever, tachycardia, and hypotension 112 days after liver transplantation. Blood tests revealed an increased inflammatory response. Computed tomography demonstrated clusters of small gas collections in the first and second lumbar vertebral bodies and the right sacral ala, a finding characteristic of the pumice stone sign of EO. Septic shock due to EO was diagnosed. The patient responded well to treatment and recovered from the infection. This case suggests that the immunosuppressive state after liver transplantation is a risk factor for EO.

COVID-19 Related Acute Respiratory Distress Syndrome versus Classical Acute Respiratory Distress Syndrome Patients: Inflammatory Biomarkers as Predictors of Mortality in Pulmonary Septic Shock.

Introduction and Objectives: Coronavirus disease-2019 (COVID-19)-related severe acute respiratory distress syndrome (ARDS) differs pathophysiological from other pulmonary septic shock-related ARDS. Thus, we assessed whether all-cause in-hospital mortality differs for severe COVID-19-related and classical severe ARDS and which inflammatory biomarkers can predict mortality among these patients. Material and Methods: This single-center, retrospective, observational cohort study included pulmonary septic shock patients (n = 114) with COVID-19-related and classical severe ARDS admitted in the Intensive Care Unit. Results: Patients with a mean age of 73 (IQR 62-82), predominantly male (63%), were divided into two groups based on outcomes: survivors (n = 50) and non-survivors (n = 64). COVID-19-related severe ARDS (n = 48) accounts for 75% of deaths. Present comorbidities like heart disease (p = 0.043), neurologic disorders (p = 0.018), and liver disease (p = 0.038) were associated with in-hospital mortality, as well. Regarding inflammatory biomarkers, the AUC/c-statistic was 0.656 (95% CI: 0.53-0.759) for leukocytes, 0.613 (95% CI: 0.509-0.717) C-reactive protein (CRP) and 0.651 (95% CI: 0.548-0.753) for procalcitonin in predicting all-cause in-hospital mortality among patients with pulmonary septic shock and severe ARDS. Conclusion: Patients with pulmonary septic shock and with COVID-19-related severe ARDS had a higher incidence of in-hospital mortality than those with classical severe ARDS. The high value of leukocytes, C-reactive protein, and procalcitonin were predictive for all-cause in-hospital mortality in patients with pulmonary septic shock and ARDS. Infection with COVID-19 was an independent predictor of in-hospital mortality in the presence of ARDS.

Is choice of approach associated with risk of avascular necrosis in pediatric septic hip?

Purpose: Septic arthritis of the hip in children and adolescents is a common condition requiring timely diagnosis and intervention. Surgical irrigation and debridement is typically performed through the anterior approach because of concerns about injury to the medial femoral circumflex artery leading to avascular necrosis. While there are multiple studies investigating the sequelae of anterior and medial approaches for reduction of developmental dislocation of the hip, none have compared these approaches for the pediatric septic hip. We hypothesize that there will be no significant difference in the rate of avascular necrosis when comparing the medial and anterior approaches to the septic hip in pediatric patients. Methods: A retrospective review was performed of pediatric septic hips treated with irrigation and debridement through either a medial or anterior approach at a single institution over an 18-year period of time. The primary outcome measure was the development of avascular necrosis. Results: Thirteen of 164 patients (7.9%) developed avascular necrosis. Avascular necrosis was noted in 9 of 101 patients who had anterior approach and 4 of 63 patients who underwent medial approach (p = 0.76). The average age for patients developing avascular necrosis was 10.0 years old versus 6.8 years old in patients who did not develop avascular necrosis (p = 0.01). The average follow-up was 3.3 years in patients with avascular necrosis versus 1.5 years for patients who did not develop avascular necrosis (p = 0.01). Conclusion: Medial approach to the pediatric septic hip does not increase the rate of avascular necrosis compared to the anterior approach. Level of evidence: Retrospective comparison study, Level III.

In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.

BACKGROUND: High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. METHODS AND RESULTS: Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 µg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. CONCLUSIONS: Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Formation of Single-Species and Multispecies Biofilm by Isolates from Septic Transfusion Reactions in Platelet Bag Model.

During 2018-2021, eight septic transfusion reactions occurred from transfusion of platelet units contaminated with Acinetobacter spp., Staphylococcus saprophyticus, Leclercia adecarboxylata, or a combination of those environmental organisms. Whether biofilm formation contributed to evasion of bacterial risk mitigations, including bacterial culture, point-of-care testing, or pathogen-reduction technology, is unclear. We designed a 12-well plate-based method to evaluate environmental determinants of single-species and multispecies biofilm formation in platelets. We evaluated bacteria isolated from septic transfusion reactions for biofilm formation by using crystal violet staining and enumeration of adherent bacteria. Most combinations of bacteria had enhanced biofilm production compared with single bacteria. Combinations involving L. adecarboxylata had increased crystal violet biofilm production and adherent bacteria. This study demonstrates that transfusion-relevant bacteria can produce biofilms well together. More work is needed to clarify the effect of biofilms on platelet bacterial risk control strategies, but US Food and Drug Administration-recommended strategies remain acceptable.

Removal of circulating mitochondrial N-formyl peptides via immobilized antibody therapy restores sepsis-induced neutrophil dysfunction.

During recovery from septic shock, circulating mitochondrial N-formyl peptides (mtFPs) predispose to secondary infection by occupying formyl peptide receptor 1 (FPR1) on the neutrophil (polymorphonuclear leukocyte, PMN) membrane, suppressing cytosolic calcium ([Ca2+]i)-dependent responses to secondarily encountered bacteria. However, no study has yet investigated therapeutic clearance of circulating mtFPs in clinical settings. Thus, we studied how to remove mtFPs from septic-shock plasma and whether such removal could preserve cell-surface FPR1 and restore sepsis-induced PMN dysfunction by normalizing [Ca2+]i flux. In in vitro model systems, mtFP removal rescued PMN FPR1-mediated [Ca2+]i flux and chemotaxis that had been suppressed by prior mtFP exposure. However, PMN functional recovery occurred in a stepwise fashion over 30 - 90 minutes. Intracellular Ca2+-calmodulin appears to contribute to this delay. In ex vivo model systems using blood samples obtained from patients with septic shock, anti-mtFP antibodies alone failed to eliminate mtFPs from septic-shock plasma or inhibit mtFP activity. We therefore created a beads-based anti-mtFP antibody cocktail (bb-AMfpA) by combining protein A/sepharose with antibodies specific for the most potent human mtFP chemoattractants. The bb-AMfpA treatment successfully removed those active mtFPs from septic-shock plasma. Furthermore, the bb-AMfpA treatment significantly restored chemotactic and bactericidal dysfunction of PMNs obtained from patients with septic shock who developed secondary infections. By clearing circulating mtFPs, the immobilized anti-mtFP antibody therapy prevented mtFP interactions with surface FPR1, thereby restoring [Ca2+]i-dependent PMN antimicrobial function in clinical septic-shock environments. This approach may help prevent the development of secondary, nosocomial infections in patients recovering from septic shock.

Assessment of acute neuronal injury in critical illness: prognostication in septic shock patients - preliminary study in a Polish population.

INTRODUCTION: Sepsis-associated brain dysfunction is a common organ dysfunction in sepsis. The main goal of this study was to verify whether the combined assessment of central nervous system injury markers (i.e. S100B, NSE, GFAP) and disease severity as per the Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) classification systems, would increase the accuracy of death prediction in septic shock. MATERIAL AND METHODS: Markers of neuronal damage were determined in 55 patients diagnosed with septic shock with no previous neurological disease. Clinical data was collected and the scores on the APACHE II, SAPS II and SOFA prognostic scales were calculated. Death before discharge from the Intensive Care Unit (ICU) was established as the endpoint. RESULTS: Nineteen patients (35%) died before ICU discharge. Patients who died had significantly higher S100B and NSE values, and APACHE II, SAPS II and SOFA scores (P< 0.05 for all). At the time of septic shock diagnosis, NSE levels more accurately predicted the risk of death before ICU discharge than S100B. However, NSE had no better predictive value for short-term mortality than APACHE II, SAPS II and SOFA. Adding C-reactive protein (CRP) and S100B concentrations to the APACHE II score created a predictive model with 95% mortality accuracy (AUC = 0.95; 95%CI 0.85-0.99; P = 0.03). CONCLUSIONS: The assessment of acute neuronal injury plays an important role in prognostication in patients with septic shock. The concentration of S100B protein in combination with APACHE II score and concentration of CRP more accurately predicts mortality than the APACHE II alone.

Apelin-13 administration allows for norepinephrine sparing in a rat model of cecal ligation and puncture-induced septic shock.

BACKGROUND: Infusion of exogenous catecholamines (i.e., norepinephrine [NE] and dobutamine) is a recommended treatment for septic shock with myocardial dysfunction. However, sustained catecholamine infusion is linked to cardiac toxicity and impaired responsiveness. Several pre-clinical and clinical studies have investigated the use of alternative vasopressors in the treatment of septic shock, with limited benefits and generally no effect on mortality. Apelin-13 (APL-13) is an endogenous positive inotrope and vasoactive peptide and has been demonstrated cardioprotective with vasomodulator and sparing life effects in animal models of septic shock. A primary objective of this study was to evaluate the NE-sparing effect of APL-13 infusion in an experimental sepsis-induced hypotension. METHODS: For this goal, sepsis was induced by cecal ligation and puncture (CLP) in male rats and the arterial blood pressure (BP) monitored continuously via a carotid catheter. Monitoring, fluid resuscitation and experimental treatments were performed on conscious animals. Based on pilot assays, normal saline fluid resuscitation (2.5 mL/Kg/h) was initiated 3 h post-CLP and maintained up to the endpoint. Thus, titrated doses of NE, with or without fixed-doses of APL-13 or the apelin receptor antagonist F13A co-infusion were started when 20% decrease of systolic BP (SBP) from baseline was achieved, to restore SBP values ≥ 115 ± 1.5 mmHg (baseline average ± SEM). RESULTS: A reduction in mean NE dose was observed with APL-13 but not F13A co-infusion at pre-determined treatment time of 4.5 ± 0.5 h (17.37 ± 1.74 µg/Kg/h [APL-13] vs. 25.64 ± 2.61 µg/Kg/h [Control NE] vs. 28.60 ± 4.79 µg/Kg/min [F13A], P = 0.0491). A 60% decrease in NE infusion rate over time was observed with APL-13 co-infusion, (p = 0.008 vs NE alone), while F13A co-infusion increased the NE infusion rate over time by 218% (p = 0.003 vs NE + APL-13). Associated improvements in cardiac function are likely mediated by (i) enhanced left ventricular end-diastolic volume (0.18 ± 0.02 mL [Control NE] vs. 0.30 ± 0.03 mL [APL-13], P = 0.0051), stroke volume (0.11 ± 0.01 mL [Control NE] vs. 0.21 ± 0.01 mL [APL-13], P < 0.001) and cardiac output (67.57 ± 8.63 mL/min [Control NE] vs. 112.20 ± 8.53 mL/min [APL-13], P = 0.0036), and (ii) a reduced effective arterial elastance (920.6 ± 81.4 mmHg/mL/min [Control NE] vs. 497.633.44 mmHg/mL/min. [APL-13], P = 0.0002). APL-13 administration was also associated with a decrease in lactate levels compared to animals only receiving NE (7.08 ± 0.40 [Control NE] vs. 4.78 ± 0.60 [APL-13], P < 0.01). CONCLUSION: APL-13 exhibits NE-sparing benefits in the treatment of sepsis-induced shock, potentially reducing deleterious effects of prolonged exogenous catecholamine administration.

A Multidisciplinary Approach to Staphylococcus aureus Triple-Valve Infective Endocarditis With Multi-Organ Involvement.

Multivalvular endocarditis is a rare and potentially fatal complication that can occur in people who inject drugs. Currently, there are few cases that have been studied or reported in literature. A complication of this manifestation that worsens prognosis and treatment is the distribution of septic emboli throughout the body which highlights the dissemination of the infection. There are no specific guidelines on the treatment of multivalvular endocarditis, but its complexity can present challenges in administering medical and surgical treatment. In this case of a 37-year-old man with infective endocarditis of 3 valves, a comprehensive work-up found septic emboli in the lungs, kidneys, ribs, spine, and brain with ophthalmologic involvement that resulted in visual impairment. This case highlights important complications that can occur with septic emboli and management of these issues using a multidisciplinary approach including the treatment of substance use disorder.

Extracorporeal Membrane Oxygenation as Circulatory Support in Adult Patients with Septic Shock: A Systematic Review.

Introduction: The utilization of extracorporeal membrane oxygenation (ECMO) in adult patients experiencing septic shock is a subject of ongoing debate within the medical community. This study aims to comprehensively address this issue through a systematic review conducted in accordance with the PRISMA guidelines. Aim of Study: The primary objective of this study is to assess the outcomes of ECMO utilization in adult patients diagnosed with septic shock, thereby providing insights into the potential benefits and uncertainties associated with this treatment modality. Materials and Methods: Our research encompassed a thorough search across electronic databases for relevant English-language articles published up until April 2023. The inclusion criteria were based on studies reporting on ECMO usage in adult patients with septic shock. Among the eligible studies meeting these criteria, a total of eleven were included in our analysis, involving a cohort of 512 patients. The mean age of the participants was 53.4 years, with 67.38% being male. Results: In the pooled analysis, the mean survival rate following ECMO treatment was found to vary significantly across different ECMO modalities. Patients receiving venovenous-ECMO (VV-ECMO) and veno-venous-arterial ECMO (VVA-ECMO) demonstrated higher survival rates (44.5% and 44.4%, respectively) compared to those receiving venoarterial-ECMO (VA-ECMO) at 25% (p<0.05). A chi-square test of independence indicated that the type of ECMO was a significant predictor of survival (χ2(2) = 6.63, p=0.036). Additionally, patients with septic shock stemming from respiratory failure demonstrated survival rates ranging from 39% to 70%. Predictors of mortality were identified as older age and the necessity for cardiopulmonary resuscitation (CPR). Conclusions: In septic shock patients, ECMO outcomes align with established indications like respiratory and cardiogenic shock. VV-ECMO and VVA-ECMO suggest better prognoses, though the optimal mode remains uncertain. Patient selection should weigh age and CPR need. Further research is vital to determine ECMO's best approach for this population.

Clinical characteristics of neonatal and infant osteomyelitis and septic arthritis: a multicenter retrospective study

Abstract Objective: Signs and symptoms of osteomyelitis or septic arthritis in neonates and infants are often nonspecific and early-stage bone infections in infants may often go unnoticed. The objective of this study was to analyze the clinical characteristics of newborns and infants with osteomyelitis and septic arthritis to improve understanding of the disorder and to assist clinicians with diagnosis. Methods: A retrospective multicenter study was conducted on neonates (0-28 days old, n = 94) and infants (1-12 months old, n = 415) with osteoarticular infections. Data consisting of clinical characteristics, complications, laboratory outcomes, and the pathogenic microorganisms causing osteomyelitis were tabulated. The statistics were further broken down into two regions and the significant differences between neonates and infants were evaluated and compared to the literature. Results: Compared to infants, neonates had significantly lower incidences of fever (p < 0.0001), higher incidences of localized swelling (p = 0.0021), higher rate of infection at the humerus (p = 0.0016), higher percentage of Escherichia coli (p < 0.0001) and Klebsiella pneumoniae (p = 0.0039) infections, lower percentage of Staphylococcus aureus infections (p < 0.0001) and were more likely to develop septic arthritis (p < 0.0001). Conclusion: Distinct differences were found between neonatal and infants with osteoarticular infections. Future studies should focus on improving diagnosis and subsequent treatment regimens for younger age groups.

CO2 gap changes compared with cardiac output changes in response to intravenous volume expansion and/or vasopressor therapy in septic shock.

Background: The difference in partial pressure of carbon dioxide (PCO2) between mixed or central venous blood and arterial blood, known as the ∆PCO2 or CO2 gap, has demonstrated a strong relationship with cardiac index during septic shock resuscitation. Early monitoring of the ∆PCO2 can help assess the cardiac output (CO) adequacy for tissue perfusion. Objectives: To investigate the value of ∆PCO2 changes in early septic shock management compared with CO. Methods: This observational prospective study included 76 patients diagnosed with septic shock admitted to Cairo University Hospital's Critical Care Department between December 2020 and March 2022. Patients were categorised by initial resuscitation response, initial ∆PCO2 and 28-day mortality. The primary outcome was the relationship between the ∆PCO2 and CO changes before and after initial resuscitation, with secondary outcomes including ICU length of stay (LOS) and 28-day mortality. Results: Peri-resuscitation ∆PCO2 changes predicted a ≥15% change in the cardiac index (CI) (area under the curve (AUC) 0.727; 95% CI 0.614 - 0.840) with 66.7% sensitivity and 62.8% specificity. The optimal ∆PCO2 change cut-off value was <-1.85, corresponding to a <-22% threshold for a 15% cardiac index increase. The PCO2 gap ratio (gap/gap ratio of T1- PCO2 gap to T0 -PCO2 gap) also predicted a ≥15% change in cardiac index (AUC 745; 95% CI 0.634 - 0.855) with 63.6% sensitivity and 79.1% specificity. The optimal CO2 gap/gap ratio cut-off value was <0.71. A significant difference in 28-day mortality was noted based on the gap/gap ratio. Conclusion: Peri-resuscitation ∆PCO2 and the gap/gap ratio are useful non-invasive bedside markers for predicting changes in CO and preload responsiveness. Contribution of the study: The current study provides an insight to the PCO2 gap changes during and after early resuscitation of septic shock patients, which correlate to cardiac output changes and might also serve as a fluid responsiveness indicator.

Functional Articulating Antibiotic Spacers for Chronic Native Septic Knee Arthritis.

Background: Semipermanent functional spacers are now utilized for prosthetic joint infection in an attempt to avoid another surgery with 2-stage treatment. This study evaluates the results of metal-on-polyethylene articulating spacers for the treatment of chronic native septic knee arthritis. Methods: This is a retrospective review of 18 patients treated with metal-on-polyethylene articulating antibiotic spacers constructed with all-polyethylene tibial components or with polyethylene inserts (PIs) with Steinmann pins or screws for chronic native knee infection. Demographic information, spacer construct type, prior knee surgery, complications, infecting organisms, infection eradication, and functional results were analyzed. Results: Of 18, 8 (44%) spacers were all-polyethylene tibial components and 10 (56%) were PI. Of 18 patients, 5 (28%) experienced spacer complications. Of 18 patients, 12 (67%) underwent a second reimplantation surgery (mean 106 days), while 6 (33%) retained their spacer (average duration 425 days). The PI group performed better in Knee Injury and Osteoarthritis Outcome score for Joint Replacement according to minimum clinically important difference and patient acceptable symptom state (PASS) criteria. The overall reimplantation group achieved Knee Injury and Osteoarthritis Outcome score for Joint Replacement PASS criteria and minimum clinically important difference criteria, while the maintained articulating spacer group did not achieve PASS criteria; however, they did reach minimum clinically important difference. Conclusions: Functional articulating spacers are a viable treatment for chronic, native knee septic arthritis. The PI patient group had a greater improvement in Knee Injury and Osteoarthritis Outcome score for Joint Replacement scores and had no significant difference in reimplantation rate as the all-polyethylene tibial components patient group. Both planned 2-stage reimplantation and longer-term spacer retention show promising results for this difficult clinical problem.

Effect of Antibiotic Therapy Before Arthrocentesis on Synovial Fluid Cell Count and Differential for Diagnosis of Native Joint Septic Arthritis.

We examined the effect of preoperative antibiotic exposure and duration on synovial fluid samples from patients with native joint septic arthritis of the hip/knee. While exposure before diagnostic arthrocentesis did not affect fluid parameters, increased duration was associated with a decreased total nucleated cell count, underscoring the complex antibiotic effects on synovial fluid parameters.