Immune-response gene 1 deficiency aggravates inflammation-triggered cardiac dysfunction by inducing M1 macrophage polarization and aggravating Ly6Chigh monocyte recruitment.

The immune response gene 1 (IRG1) and its metabolite itaconate are implicated in modulating inflammation and oxidative stress, with potential relevance to sepsis-induced myocardial dysfunction (SIMD). This study investigates their roles in SIMD using both in vivo and in vitro models. Mice were subjected to lipopolysaccharide (LPS)-induced sepsis, and cardiac function was assessed in IRG1 knockout (IRG1-/-) and wild-type mice. Exogenous 4-octyl itaconate (4-OI) supplementation was also examined for its protective effects. In vitro, bone marrow-derived macrophages and RAW264.7 cells were treated with 4-OI following Nuclear factor, erythroid 2 like 2 (NRF2)-small interfering RNA administration to elucidate the underlying mechanisms. Our results indicate that IRG1 deficiency exacerbates myocardial injury during sepsis, while 4-OI administration preserves cardiac function and reduces inflammation. Mechanistic insights reveal that 4-OI activates the NRF2/HO-1 pathway, promoting macrophage polarization and attenuating inflammation. These findings underscore the protective role of the IRG1/itaconate axis in SIMD and suggest a therapeutic potential for 4-OI in modulating macrophage responses.

Sintilimab-induced myocarditis suspected in a patient with esophageal cancer and followed septic shock: case report and literature review.

Background: Immune checkpoint inhibitors (ICIs) have become a prevalent tool in anti-tumor therapy in recent years. They may cause immune-related adverse events (irAEs) including potentially life-threatening cardiovascular toxicities such as myocarditis. Case presentation: In this report, we describe a 69-year-old man with recurrent esophageal cancer who developed myocarditis after receiving three cycles of sintilimab combined with nab-paclitaxel. Despite a rising cardiac troponin I (cTnI), he initially reported no discomfort. He was later suspected of having with sintilimab-induced myocarditis. Although treatment with methylprednisolone reduced his cTnI levels, he still experienced significant discomfort. Moreover, he developed pneumonia and septic shock. Conclusion: In our literature search to identify all reported cases of sintilimab-associated adverse events involving myocarditis, we found 14 patients, including those with esophageal cancer, thymoma, lung cancer, gastric cancer, hepatobiliary carcinoma, and chordoma. The primary treatment for ICI-induced cardiotoxicity is methylprednisolone. However, the long-term or high-dose use of steroids can also induce side effects, which have not been the focus of these case reports. This is the first reported case of asymptomatic immune-mediated myocarditis occurring during the treatment of esophageal cancer with sintilimab. It is also the first to address the side effects of methylprednisolone used in the treatment of sintilimab-related myocarditis. To facilitate an early diagnosis, regular monitoring is required during sintilimab treatment. We should also focus on the prevention and management of adverse effects related to steroid use.

Association between heart rate and mortality in patients with septic shock: an analysis revealed by time series data.

BACKGROUND: Heart rate is crucial for patients with septic shock, but there are few studies on the scope of heart rate. Therefore, we studied the relationship between different heart rates and mortality of critically ill patients with septic shock, and explored the optimal heart rate range, in order to provide new insights for clinical treatment of septic shock. METHODS: This retrospective study utilized time-series heart rate data from the Medical Information Mart for Intensive Care (MIMIC) IV database. Patients with septic shock were identified as the Sepsis 3.0 criteria and received vasopressor therapy in the first 24 h since ICU admission. We calculated the time-weighted average heart rate (TWA-HR) based on the time-series data. The restricted cubic spline (RCS) analysis was employed to investigate the nonlinear relationship between heart rate and 28-day mortality, aiming to explore the optimal heart rate control target for septic patients and using this target as the exposure factor. The primary outcome was 28-day mortality, and the secondary outcome were ICU and in-hospital mortality. For the original cohort, we applied the log-rank test to infer the relationship between heart rate and mortality. To control for bias introduced by confounders, we utilized propensity score matching (PSM) to reduce imbalances between normal TWA-HR and high TWA-HR groups, and we established a series of models [the multivariable Cox model, matching weight (MW)-adjusted Cox model, multivariable logistic regression, MW-adjusted logistic regression, and doubly robust model] as sensitivity analyses and subgroup analyses to demonstrate the robustness of our findings. RESULTS: A total of 13492 patients were included in our study. The RCS analysis based on Cox and logistic regression showed increased risk of mortality (P < 0.001, non-linear P < 0.001) when TWA-HR > 85 beats per minute (bpm). The log-rank test revealed in terms of the 28-day mortality, the hazard ratio (HR) (95% confidence interval [CI]) was 1.92 (1.78-2.06, P < 0.001) for patients with high TWA-HR compared to normal TWA-HR group. Similarly, for the ICU mortality, the HR (95% CI) was 1.64 (1.52-1.78, P < 0.001), and for the in-hospital mortality, the HR (95% CI) was 1.61 (1.48-1.76, P < 0.001). Collectively, the sensitivity analysis consistently demonstrated higher 28-day mortality, ICU mortality, and in-hospital mortality in patients with TWA-HR > 85 bpm. CONCLUSION: Patients with septic shock whose heart rate was controlled no more than 85 bpm during ICU stay received survival benefit in terms of 28-day, ICU and in-hospital mortality. .

Diagnostic accuracy of point-of-care ultrasound (PoCUS) for the diagnosis of hip effusion in the pediatric emergency department.

PURPOSE: A new limp or refusal to weight-bear are common symptoms in children presenting to the pediatric emergency department (ED). This poses a diagnostic challenge, particularly among toddlers and nonverbal patients. Point-of-care ultrasound (PoCUS) used by pediatric emergency medicine physicians may detect hip effusion, which dramatically aids diagnostic workup and management. There is limited literature regarding the accuracy of hip PoCUS conducted by pediatric emergency medicine physicians. This study aims to assess the diagnostic performance of pediatric emergency medicine physician-performed PoCUS in identifying hip effusion. METHODS: This prospective study was conducted in a single-center pediatric ED. Children presenting with limb pain or new limp were evaluated by pediatric emergency medicine physicians who also performed hip PoCUS and categorized findings as either "effusion" or "no effusion" based on standard sonographic definitions. Patients also underwent radiology department ultrasound reviewed by a pediatric radiologist. Diagnostic test characteristics with corresponding 95% confidence intervals (CI) were calculated using radiology department ultrasound findings as the reference standard. RESULTS: A total of 95 patients were enrolled by 8 pediatric emergency medicine physicians. Excellent agreement was observed between PoCUS performed by pediatric emergency medicine physicians and radiology department ultrasound for the presence or absence of hip effusion (kappa = 0.81 [95% CI 0.70-0.93]). Hip effusion was identified by PoCUS in 44 out of 49 effusion-positive patients, with a sensitivity of 89.8% (95% CI 77.7-96.6%), specificity of 91.3% (95% CI 79.2%-97.5%), positive likelihood ratio of 10.33 (95% CI 4.03-26.47), and negative likelihood ratio of 0.11 (95% CI 0.05-0.26). CONCLUSION: PoCUS performed by pediatric emergency medicine physicians has reasonably high sensitivity and specificity for diagnosing hip effusion among pediatric patients presenting to the pediatric ED with a limp or leg pain. This practice may potentially expedite both diagnosis and treatment within this patient population.

RéSUMé: OBJECTIF: Un nouveau boiteux ou un refus de porter le poids sont des symptômes courants chez les enfants qui se présentent à l'urgence pédiatrique (DE). Cela pose un défi diagnostique, en particulier chez les enfants en bas âge et les patients non verbaux. Les échographies de point de soins (PUCU) utilisées par les médecins des urgences pédiatriques peuvent détecter un épanchement de la hanche, ce qui facilite considérablement le diagnostic et la gestion. Il existe une littérature limitée concernant la précision des PUC de la hanche effectuée par les médecins urgentistes pédiatriques. Cette étude vise à évaluer la performance diagnostique des PUCU réalisées par un médecin en médecine d'urgence pédiatrique pour identifier l'effusion de la hanche. MéTHODES: Cette étude prospective a été menée dans un seul centre de DE pédiatrique. Les enfants présentant une douleur aux membres ou une nouvelle boiterie ont été évalués par des médecins pédiatriques d'urgence qui ont également effectué un PUCU de la hanche et ont classé les résultats comme "épanchement" ou "aucun épanchement" selon les définitions échographiques standard. Les patients ont également subi une échographie du service de radiologie examinée par un radiologue pédiatrique. Les caractéristiques des tests diagnostiques avec leurs intervalles de confiance (IC) correspondants à 95 % ont été calculées en utilisant les résultats d'échographie du service de radiologie comme norme de référence. RéSULTATS: Un total de 95 patients a été inscrits par huit médecins urgentistes pédiatriques. Une excellente concordance a été observée entre les ultrasons réalisés par les médecins pédiatriques d'urgence et ceux du service de radiologie pour la présence ou l'absence d'effusion de la hanche (kappa = 0.81 [IC à 95% 0.70­0.93]). Le épanchement de la hanche a été identifié par PUCU chez 44 des 49 patients ayant un épanchement positif, avec une sensibilité de 89,8 % (IC à 95%, 77.7 ­96.6 %), une spécificité de 91,3 % (IC à 95%, 79.2­97.5%), un rapport de vraisemblance positif de 10,33 (IC à 95 %, 4.03­26.47) et un rapport de vraisemblance négatif de 0,11 (IC à 95% 0.05-0.26) CONCLUSIONS: Le PUCU réalisé par des médecins pédiatriques d'urgence a une sensibilité et une spécificité raisonnablement élevées pour diagnostiquer l'épanchement de la hanche chez les patients pédiatriques présentant une lésion ou une douleur aux jambes. Cette pratique pourrait accélérer le diagnostic et le traitement dans cette population de patients.

Outcomes of One-Stage Arthroscopic Ankle and Tibiotalocalcaneal Arthrodesis with External Fixation for Septic Ankle and Hindfoot Arthritis: A Case-Series Study.

OBJECTIVES: The occurrence of infection in the ankle and hindfoot presents a formidable surgical challenge. Currently, there is a lack of consensus regarding its treatment strategies. The purpose of this study was to investigate the outcomes of one-stage arthroscopic ankle and tibiotalocalcaneal (TTC) arthrodesis with external fixation in the treatment of septic ankle and hindfoot arthritis. METHODS: A retrospective consecutive case-series study was conducted involving six patients diagnosed with acute or chronic septic ankle or hindfoot arthritis, who underwent operative intervention entailing thorough debridement, arthroscopically assisted one-stage ankle or TTC fusion, and external fixation. The American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot score and visual analog scale (VAS) pain score were determined preoperatively and at the final follow-up. Demographic and clinical data, inclusive of perioperative and postoperative complications, were recorded. Comparisons of AOFAS ankle-hindfoot score and VAS pain score between preoperative measures and those at the final follow-up were conducted using paired t-tests or paired Wilcoxon rank-sum tests. RESULTS: The study cohort comprised two males and four females, with a mean age of 48.7 years (range, 26-75) at the time of surgical intervention. At the final follow-up (mean, 26.5 months; range, 16-48), the AOFAS scores exhibited a significant improvement, ascending from an initial mean of 38.8 (range, 12-57) to 80.0 (range, 54-92) (p = 0.007). VAS scores indicated a substantial reduction in pain, decreasing from 6.5 (range, 4-9) to 0 (range, 0-5) (p = 0.046). All patients had achieved osseous consolidation, with a hindfoot infection control rate of 100%. CONCLUSION: One-stage arthroscopic ankle and TTC arthrodesis with external fixation is as an effective therapeutic choice for septic ankle or hindfoot arthritis. This approach yields favorable outcomes characterized by effective infection control, favorable osseous consolidation, and significant functional restoration of the affected limb.

Pathophysiology and Evolving Treatment Options of Septic Arthritis: A Narrative Review.

Pyogenic (septic) arthritis is a severe joint infection characterized by the invasion of microorganisms into the synovium, causing inflammation and joint destruction. This review article provides a comprehensive overview of pyogenic arthritis, focusing on etiology, pathogenesis, clinical manifestations, diagnosis, and management strategies. This review explores routes of microbial entry into joints, emphasizing the importance of prompt identification and treatment to prevent irreversible joint damage. Clinical manifestations, such as joint pain, swelling, and limited range of motion, are discussed, along with the challenges in differentiating pyogenic arthritis from other joint disorders. Diagnostic approaches, including joint aspiration and imaging modalities, are critically examined for accuracy in confirming diagnosis. This review also addresses the significance of early intervention through antimicrobial therapy and joint drainage, highlighting the role of multidisciplinary collaboration in optimizing patient outcomes. In summary, the present investigation underscores the complexities of pyogenic arthritis and the need for a comprehensive understanding of pathophysiology for timely and effective management to improve patient prognosis and quality of life.

Escherichia coli ST1193 O75 H5: A rare cause of native valve endocarditis with multifocal emboli to brain and spleen.

Escherichia coli (E. coli) is a facultative anaerobic gram-negative rod bacterium, which can acquire pathogenicity through the acquisition of additional genetic material. We present a case of E. coli ST1193, an emerging global multidrug-resistant (MDR) high-risk clone, causing native valve endocarditis and septic brain and splenic emboli in a 67-year-old woman.

The efficacy, safety and effectiveness of hyperoncotic albumin solutions in patients with sepsis: A systematic review and meta-analysis.

Background: Intravenous fluid therapy is a ubiquitous intervention for the management of patients with sepsis, however excessive cumulative fluid balance has been shown to result in worse outcomes. Hyperoncotic albumin is presented in low volumes, is an effective resuscitation fluid and may have effects beyond plasma volume expansion alone. This systematic review aimed to assess the efficacy, safety and effectiveness of hyperoncotic albumin solutions in the management of sepsis. Methods: We searched four databases and two trial registries for controlled clinical trials of hyperoncotic albumin for management of sepsis. Review outcomes were mortality, need for renal replacement therapy, cumulative-fluid balance, and need for organ support. We used methods guided by the Cochrane Handbook for reviews of clinical interventions. Studies were assessed using Cochrane's Risk of Bias 2 tool. We performed pairwise meta-analysis where possible. Certainty of evidence was assessed using GRADE. Results: We included six trials; four (2772 patients) were meta-analysed. Most studies had moderate or high risk of bias. There was no significant difference in 28-day mortality for septic patients receiving hyperoncotic albumin compared to other intravenous fluids (OR 0.95, [95% CI: 0.8-1.12]); in patients with septic shock (2013 patients) there was a significant reduction (OR 0.82 [95% CI: 0.68-0.98]). There was no significant difference in safety outcomes. Hyperoncotic albumin was associated with variable reduction in early cumulative fluid balance and faster resolution of shock. Conclusions: There is no good-quality evidence to support the use of hyperoncotic albumin in patients with sepsis, but it may reduce short-term mortality in the sub-groups with septic shock. It appears safe in terms of need for renal replacement therapy and is associated with reduced early cumulative fluid balance and faster resolution of shock. Larger, better quality randomised controlled trials in patients with septic shock may enhance the certainty of these findings. Review registration: PROSPERO ref: CRD42021150674.

Pre-hospital 'dirty adrenaline': A descriptive case series of patients receiving peripheral dilute adrenaline infusions in Central Australian remote nurse-led clinics prior to aeromedical retrieval.

OBJECTIVES: 'Dirty adrenaline' is the informal term used for a rapidly made peripheral dilute adrenaline infusion in the emergency treatment of shock, most commonly 1 mg adrenaline in 1 L 0.9% NaCl. It has long been part of the remote clinician's arsenal despite no supporting scientific literature. Remote clinics in Central Australia can be hours away from critical care support. The region's high prevalence of renal and cardiac disease means that access to early vasopressors and inotropes is a necessity for treating shock. To tackle this, remote clinicians often use 'dirty adrenaline'. We present a review of 'dirty adrenaline' use in this region. METHODS: Central Australian Retrieval Service's database was screened to identify cases in which a peripheral dilute adrenaline infusion was administered in a remote clinic prior to patient aeromedical retrieval. A retrospective chart review collected: patient demographics; clinical characteristics; infusion details; adverse events; hospital lengths of stay; and mortality outcomes. RESULTS: Fifty-seven cases were identified. Median patient age was 50 (range: 2-96). Septic shock was the most common clinical indication (40/57). Median infusion duration was 155 min. Median systolic BP from commencement until retrieval increased from 75.5 to 91 mmHg. Survival to hospital discharge was 86% (49/57). No significant adverse events associated with 'dirty adrenaline' were recorded. CONCLUSION: 'Dirty adrenaline' is safe to administer and appears to considerably improve survival when used to treat fluid-resistant shock in remote nurse-led clinics guided by an off-site critical care physician.

Evaluation of Sepsis-Related Medical Emergency Team (MET) Calls with Pharmacist Involvement and Time to Antimicrobial Administration.

Objective: To evaluate the difference in proportion of patients receiving antimicrobials within one hour of sepsis recognition at sepsis-related Medical Emergency Team (MET) calls, without or with a sepsis-credentialed pharmacist. Design: Retrospective pre and post-intervention study. Setting: Single centre tertiary referral hospital. Participants: Patients admitted to the General Medicine Unit who had a sepsis-related MET call 24 hrs per day, and all other units from 17:00-08:00 hrs from August 2019 to Jan 2020 in the pre-intervention cohort and Aug 2020 to Jan 2021 for the post-intervention cohort. Interventions: Pharmacists attended MET calls to assist selection of antimicrobials, collaboratively prescribe with the medical officers, ensure supply, provide advice on dosing calculations, reconstitution, and administration. The pre-intervention cohort (Aug 2019-Jan 2020) did not have credentialed pharmacists' involvement at MET calls. Outcome Measures: Proportion of patients who received antimicrobials within one hours of MET call. Results: There were 97 sepsis-related MET calls in the pre-intervention cohort and 110 sepsis-related MET calls in the post-intervention cohort. A significantly higher proportion of patients received antimicrobials within one hour with pharmacist involvement, compared to control (81.3% vs 59.7%, P = .0006). A reduction in median time to antimicrobial administration (43 min vs 54 min, P = .017) was observed. Conclusion: Sepsis-related MET calls with pharmacist involvement experienced a greater proportion of patients receiving antimicrobials within one hour of sepsis recognition, and a reduction in median time to antimicrobial administration. These results provide support for routine pharmacist involvement at MET calls to assist patients receiving medications in a timely and efficient manner.

Exosomal Drug Delivery Systems: A Novel Therapy Targeting PD-1 in Septic-ALI.

BACKGROUND: The cytokine storm triggered by sepsis can lead to the development of acute lung injury (ALI). Human umbilical cord Mesenchymal stem cells derived exosomes (HucMSCs-EXOs) have been demonstrated to possess immunosuppressive and anti-inflammatory properties. Programmed cell death receptor 1 (PD-1) plays a crucial role in maintaining the inflammatory immune homeostasis. The aim of this study is to investigate the synergistic therapeutic effect of EXOs loaded with anti-PD-1 peptide on septic-ALI. METHODS: This study prepares a novel EXOs-based drug, named MEP, by engineering modification of HucMSCs-EXOs, which are non-immunogenic extracellular vesicles, loaded with anti-PD-1 peptide. The therapeutic effect and potential mechanism of MEP on septic-ALI are elucidated through in vivo and in vitro experiments, providing experimental evidence for the treatment of septic acute lung injury with MEP. RESULTS: We found that, compared to individual components (anti-PD-1 peptide or EXOs), MEP treatment can more effectively improve the lung injury index of septic-ALI mice, significantly reduce the expression levels of inflammatory markers CRP and PCT, as well as pro-inflammatory cytokines TNF-α and IL-1ß in serum, decrease lung cell apoptosis, and significantly increase the expression of anti-inflammatory cytokine IL-10 and CD68+ macrophages. In vitro, MEP co-culture promotes the proliferation of CD206+ macrophages, increases the M2/M1 macrophage ratio, and attenuates the inflammatory response. GEO data analysis and qRT-PCR validation show that MEP reduces the expression of inflammasome-related genes and M1 macrophage marker iNOS. CONCLUSION: In both in vitro and in vivo settings, MEP demonstrates superior therapeutic efficacy compared to individual components in the context of septic-ALI.

Fludrocortisone dose-response relationship in septic shock: a randomised phase II trial.

BACKGROUND: The combination of intravenous hydrocortisone and enteral fludrocortisone may reduce mortality in patients with septic shock. The optimal dose and reliability of absorption of fludrocortisone in critically ill patients are unclear. METHODS: In a multi-centre, open label, phase II randomized clinical trial, intravenous hydrocortisone alone or in combination with one of three doses of enteral fludrocortisone (50 µg, 100 µg or 200 µg daily) for 7 days was compared in patients with septic shock. The primary outcome was time to shock resolution. We conducted pharmacokinetic studies to assess absorption. RESULTS: Out of 153 enrolled patients, 38 (25%) received hydrocortisone alone, 42 (27%) received additional 50 µg, 36 (24%) received 100 µg and 37 (24%) received 200 µg fludrocortisone. Plasma concentrations of fludrocortisone were detected in 97% of patients at 3 h-median (interquartile range [IQR]) 261 (156-334) ng/L. There was no significant difference in the time to shock resolution between groups with median (IQR) of 3 (2.5-4.5), 3 (2-4), 3 (2-6) and 3 (2-5.5) days in the hydrocortisone alone, 50 µg, 100 µg and 200 µg fludrocortisone groups, respectively. The corresponding 28-day mortality rates were 9/38 (24%), 7/42 (17%), 4/36 (11%) and 4/37 (11%), respectively. There were no significant differences between groups with respect to, recurrence of shock, indices of organ failure or other secondary outcomes. CONCLUSIONS: Enteral fludrocortisone resulted in detectable plasma fludrocortisone concentrations in the majority of critically ill patients with septic shock, although they varied widely indicating differing absorption and bioavailability. Its addition to hydrocortisone was not associated with shorter time to shock resolution.

Prognostic Value of the Lactate/Albumin Ratio for 28-Day Mortality in Pediatric Septic Shock: A Prospective Cohort Study.

Background Septic shock remains a leading cause of mortality in children. The lactate/albumin ratio (LAR) has emerged as a potential prognostic marker for mortality in septic shock, yet most existing research focuses on adults, with limited data available for pediatric populations, particularly in Vietnam. Objectives This study aims to evaluate the prognostic utility of the LAR in predicting 28-day mortality among children aged two months to 15 years with septic shock in Vietnam. Methods We conducted a prospective cohort study involving children diagnosed with septic shock at the largest pediatric intensive care unit (PICU) in the Mekong Delta, Vietnam, from July 2022 to June 2024. Clinical and laboratory parameters, including lactate and albumin levels, were measured at the time of septic shock diagnosis. Patients were followed for 28 days, with outcomes categorized as either survival or mortality. The prognostic performance of LAR was assessed through its discrimination and calibration capabilities. Results The 28-day mortality rate was 63.4%. LAR was significantly higher in non-survivors compared to survivors (p < 0.001). The area under the receiver operating characteristic curve (AUROC) for LAR was 0.91, indicating superior discriminatory power compared to lactate alone and comparable to albumin. Using a Youden index-derived cut-off of 1.84, LAR demonstrated a sensitivity of 84.6% and a specificity of 80%. Kaplan-Meier analysis and log-rank testing revealed significantly lower survival probabilities in children with LAR ≥1.84 (p < 0.05). The Hosmer-Lemeshow test confirmed good calibration of LAR in mortality prediction (p > 0.05). Conclusion The lactate/albumin ratio exhibits excellent discriminatory and calibration properties, making it a valuable tool for predicting 28-day mortality in pediatric septic shock. This ratio should be considered for routine use in clinical practice to improve prognostic assessments in this vulnerable population.

Diagnosis and treatment challenges in a rare Clostridium infection: A case report.

The Clostridium genus includes >180 species of Gram-positive, anaerobic, sporulating bacteria. Under certain conditions, these can cause a wide range of invasive infections in humans. Clostridium paraputrificum occurs in the commensal intestinal flora and related bacteremia typically occurs secondary to an injury to the intestinal mucosa and in the presence of predisposing conditions, such as gastrointestinal disorders, malignancies, diabetes, HIV infection or neutropenia. The current study presents the case of a 70-year-old male patient, a rural resident living in poverty, with a history of alchohol consumption and cardiovascular pathology. Several initial and subsequent diagnoses were ruled out by successive investigations (e.g., stroke, meningitis, localized tetanus). Blood cultures were eventually found positive for Clostridium paraputrificum and the patient developed septic shock despite treatment with metronidazole and penicillin G. Once switched to carbapenem, the patient progressed favorably, suggesting that carbapenem could work as a first-line antibiotic treatment for Clostridium paraputrificum infections.

Prevalence, risk factors, microbiological results and clinical outcome in unexpected positive intraoperative cultures in unclear and presumed aseptic hip and knee revision arthroplasties - A ten-year retrospective analysis with a minimum follow up of 2 years.

Background: The aim of this study was to assess the prevalence, microbiological spectrum, risk factors, and clinical outcomes of unexpected-positive-intraoperative-cultures (UPIC) in presumed aseptic and unclear revision-total-hip-/knee-arthroplasties (rTHA and rTKA) compared to culture-negative (CN) revisions. Methods: This study reviewed all International-consensus-meeting-2018 (ICM 2018) negative or inconclusive rTHA (n = 751) and rTKA (n = 679) performed at our institution from 2011 to 2020 with a minimum follow-up of two years. A Kaplan-Meier-analysis was performed to determine the septic and aseptic-free implant survival in cases with UPIC's and matched culture-negative cases. Patient demographics, risk factors, microbiological spectrum and clinical outcomes were evaluated. Results: There were significantly more UPIC cases in rTHA 196/751 (26.1 %) compared to rTKA 113/679 (16.6 %); (p < 0.001). UPICs in rTKA and rTHA have a lower septic and aseptic implant-free-survival compared to CN revisions. Patients with a history of nickel allergy have a higher risk of an UPIC in rTHA and rTKA (p < 0.001). Septic re-revisions after UPIC had a significantly (H: p = 0.004; K: p = 0.030) shorter time period to the primary/previous surgery (H: 84 (IQR:41-797); K: 115 (IQR:55-446)) compared to patients with aseptic re-revisions after UPIC (H:1248 (IQR:178-3534); K: 827 (IQR:361-1183)). Conclusion: UPICs have a higher rate of septic and aseptic failure than CN outcomes. UPICs are twice as common in rTHA compared to rTKA. Preoperative PJI workup reduces the UPIC rate. Nickel allergy is a risk factor for UPIC. Early revisions with UPICs after primary THA or TKA have a higher risk of septic failure. The translational potential of this article: This article provides new information on revision rates for UPIC and potential risk factors for UPIC and its treatment failure.

Ruxolitinib-based senomorphic therapy mitigates cardiomyocyte senescence in septic cardiomyopathy by inhibiting the JAK2/STAT3 signaling pathway.

Background: Cellular senescence has emerged as a pivotal focus in cardiovascular research. This study investigates the previously unrecognized role of cellular senescence in septic cardiomyopathy (SCM) and evaluates senomorphic therapy using ruxolitinib (Rux) as a potential treatment option. Methods: We employed lipopolysaccharide (LPS)-induced neonatal rat cardiomyocytes (NRCMs) and two mouse models-LPS-induced and cecal ligation and puncture (CLP)-induced SCM models-to assess Rux's effects. RNA sequencing, western blotting (WB), quantitative polymerase chain reaction (qPCR), immunofluorescence, immunohistochemistry, senescence-associated ß-galactosidase (SA-ß-gal) assay, and other techniques were utilized to investigate underlying mechanisms. Results: Senescence-associated secretory phenotype (SASP) and cellular senescence markers were markedly elevated in LPS-induced NRCMs and SCM animal models, confirmed by the SA-ß-gal assay. Rux treatment attenuated SASP in vitro and in vivo, alongside downregulation of senescence markers. Moreover, Rux-based senomorphic therapy mitigated mitochondrial-mediated apoptosis, improved cardiac function in SCM mice, restored the balance of antioxidant system, and reduced reactive oxygen species (ROS) levels. Rux treatment restored mitochondrial membrane potential, mitigated mitochondrial morphological damage, and upregulated mitochondrial complex-related gene expression, thereby enhancing mitochondrial function. Additionally, Rux treatment ameliorated SCM-induced mitochondrial dynamic dysfunction and endoplasmic reticulum stress. Mechanistically, Rux inhibited JAK2-STAT3 signaling activation both in vitro and in vivo. Notably, low-dose Rux and ABT263 showed comparable efficacy in mitigating SCM. Conclusions: This study highlighted the potential significance of cellular senescence in SCM pathogenesis and suggested Rux-based senomorphic therapy as a promising therapeutic approach for SCM.

Clinical efficacy of Xuebijing injection for the treatment of sepsis: A retrospective cohort study.

OBJECTIVE: The objective of this study was to investigate the clinical efficacy and safety of treating sepsis patients with Xuebijing injection (XBJI). METHODS: We conducted a retrospective analysis of 418 patients who experienced severe infections and were treated with XBJI from June 2018 to June 2021. Propensity score matching was used to match the patient cases. The study population included 209 pairs of cases (418 individuals), and the analysis included data from before and after a 14-day course of treatment with carbapenem alone, or carbapenem with XBJI. RESULTS: There were no significant differences in the 14-day mortality or length of hospital stay (P > 0.05) between the two groups. The combined treatment group had more patients with C-reactive protein that returned to normal levels (compared to baseline) than the non-combined treatment group (14.4% vs 8.1%; odds ratio [OR]: 0.528; 95% confidence interval [CI]: 0.282-0.991; P = 0.026). Similarly, the combined treatment group had higher procalcitonin attainment rate (55.0% vs 39.7%; OR: 0.513; 95% CI: 0.346-0.759; P = 0.001) than the non-combined treatment group. Further, more patients in the combined treatment group achieved normal creatinine levels than in the non-combined treatment group (64.1% vs 54.1%; OR: 0.659; 95% CI: 0.445-0.975; P = 0.037). CONCLUSION: The combination of XBJI with carbapenem did not reduce the 14-day mortality rate of patients with severe infection, but it was able to reduce the level of inflammatory factors in patients with sepsis, and had a protective effect on liver and kidney function. Please cite this article as: Gong ZT, Yang HX, Zhu BB, Liu HH, Siri GL. Clinical efficacy of Xuebijing injection for the treatment of sepsis: A retrospective cohort study. J Integr Med. 2024; Epub ahead of print.

Phoenix criteria for sepsis: are these enough to guide a clinician?

Sepsis is the leading cause of mortality in children worldwide. There is a paucity of data on the criteria used to define sepsis and septic shock and predict mortality. Schlapbach et al. published Phoenix criteria to define sepsis in JAMA in 2024. Previously, paediatricians have used systemic inflammatory response syndrome (SIRS) criteria, but these criteria lack sensitivity and specificity. This group recommends that sepsis in children be identified by a Phoenix Sepsis Score of at least 2 points in children with suspected infection, which indicates potentially life-threatening dysfunction of the respiratory, cardiovascular, coagulation, and/or neurological systems. Though included in the 8-point criteria, important criteria like renal and liver are missing from the main criteria. We remain worried about the way these criteria got excluded from the main criteria. Therefore, in this brief report, whilst commending the authors for this stelar task, we highlight the main pitfalls in these criteria especially the renal, neurologic, and liver criteria. These criteria have been shown to be independently associated with outcomes, and we recommend that in the future iterations of the criteria, renal and liver criteria should be defined according to latest definitions and the task force consider utilizing latest criteria for each organ system involved within the formulated criteria. CONCLUSION:  In conclusion, Phoenix criteria are a step in the right direction to define life-threatening organ dysfunction in sepsis, but clinicians need to be mindful that diagnosis/treatment of less severe sepsis should not be delayed if these criteria are not met. Therefore, local early detection and management tools for sepsis should be followed. WHAT IS KNOWN: • There has always been a quest for a definition for pediatric sepsis. There are limitations to the previous pediatric sepsis criteria which were published in 2005 by the International Pediatric Sepsis Consensus Conference (IPSCC). IPSCC defines sepsis as a suspected or confirmed infection in the presence of systemic inflammatory response syndrome (SIRS). These new Phoenix Pediatric Sepsis (PPS) criteria for sepsis and septic shock are intended to identify children with life-threatening organ dysfunction due to infection, and the score was developed based on a very large pediatric dataset. WHAT IS NEW: • Though the intention of Phoenix criteria is to help identify children with life threatening organ dysfunction, unfortunately the crietria will miss signs of early sepis. In this manuscript, we point out some of the drawbacks of these criteria which need to be borne in mind while applying these criteria.

Literature review and case report of septic arthritis and purpura fulminans leading to a child limb amputation as chickenpox complications.

Introduction and significance: Chickenpox, induced by the varicella-zoster virus (VZV), generally presents with an itchy rash and fluid-filled blisters. While complications such as pneumonia and sepsis are well-documented, occurrences of septic arthritis and purpura fulminans are exceedingly rare. Septic arthritis following varicella infection is infrequently reported and often attributed to Staphylococcus aureus. Purpura fulminans encompasses disorders characterized by rapidly progressing purpuric lesions, often fatal and associated with consumptive coagulopathy. Case presentation: The authors present the case of an 8-year-old boy diagnosed with chickenpox who concurrently developed severe left knee pain, erythema, and swelling indicative of septic arthritis, along with a single pustular lesion on his right foot that progressed to purpura fulminans. Laboratory investigations revealed elevated inflammatory markers. Knee ultrasound findings were consistent with septic arthritis, corroborated by synovial fluid analysis. Immediate initiation of empiric antibiotics was undertaken. Further investigation disclosed unusual coagulation parameters, positive autoantibodies, and reduced protein S levels. Treatment included anticoagulation, immunomodulation, and ultimately, amputation. Clinical discussion: This rare case underscores the complexity of varicella-related complications, representing the first documented instance of simultaneous septic arthritis and purpura fulminans in a pediatric patient. It highlights the necessity of a multidisciplinary approach for accurate diagnosis and management, emphasizing the importance of recognizing rare complications to improve patient outcomes. Conclusion: This case exemplifies the complexity of varicella-associated complications, showcasing a rare simultaneous occurrence of septic arthritis and purpura fulminans in a pediatric patient. It underscores the importance of a thorough understanding and collaborative management approaches for timely intervention and enhanced clinical outcomes.

Serial Trend of Neutrophil CD64, C-reactive Protein, and Procalcitonin as a Prognostic Marker in Critically Ill Patients with Sepsis/Septic Shock: A Prospective Observational Study from a Tertiary Care ICU.

Aim and background: Neutrophil CD64 (nCD64) is evolving as a prognostic biomarker in sepsis. The primary objective of this study was to evaluate whether serial trend of nCD64, procalcitonin (PCT), and C-reactive protein (CRP) predict 28-day mortality in patients with sepsis/septic shock, as per Sepsis-3 criteria. Materials and methods: This prospective, observational single-center cohort study included 60 adult patients (age ≥18 years) with sepsis. Serial biomarker levels with SOFA score were measured at admission (day 0), on day 4, and on day 8. Results: Of the 60 patients, 42 (70%) had septic shock. Biomarker levels at admission did not differ between patients with sepsis and septic shock. Thirty-seven patients survived and 23 were non-survivors by day 28. There was a significant fall in serial trend of all three biomarkers from admission till day 8 (Friedman p < 0.001) in survivors compared to a non-significant change in non-survivors. On multivariate analysis, SOFA score at admission (OR 1.731), more days with vasopressor support (OR 1.077), rise in CD64 from day 0 to day 8 (OR 1.074), and rise in CRP from day 0 to 8 (OR 1.245) were the significant predictors of 28-day mortality (p < 0.05). The highest area under the ROC curve was obtained for more days of vasopressor therapy (0.857), followed by a rise in CD64 from day 0 to day 8 (0.798). Conclusion: Serial trend of biomarkers has prognostic utility. The rise in CD64 from day 0 to day 8 was a good predictor of mortality compared to the trend of other biomarkers. How to cite this article: Patnaik R, Azim A, Singh K, Agarwal V, Mishra P, Poddar B, et al. Serial Trend of Neutrophil CD64, C-reactive Protein, and Procalcitonin as a Prognostic Marker in Critically Ill Patients with Sepsis/Septic Shock: A Prospective Observational Study from a Tertiary Care ICU. Indian J Crit Care Med 2024;28(8):777-784.