Sepsis Research Articles

Kinetics of the Lactate to Albumin Ratio in New Onset Sepsis: Prognostic Implications.

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.

Maternal Pathologies Associated with Admission to the Intensive Care Unit

Introduction: Maternal health is a global concern due to its significant impact on mothers and newborns. In developing countries, obstetric complications often lead to ICU admissions.Objective: To determine the prevalence of maternal pathologies associated with admission to the Intensive Care Unit (ICU) at the Instituto Ecuatoriano de Seguridad Social (IESS) in Manta, during the period from August 2022 to August 2023.Methods: A descriptive cross-sectional study was conducted with 13 patients admitted to the ICU for maternal pathologies. Variables analyzed included age, type of delivery, maternal pathology, and length of hospital stay.Results: Women aged 25 to 30 years represented 30.77% of ICU admissions. 76.92% of deliveries were by cesarean section. The main pathologies identified were severe preeclampsia (31.03%) and sepsis (20.69%). The duration of hospital stay ranged from three to five days in most cases.Conclusions: Adolescent women and those aged 25 to 30 are most likely to require intensive care. Severe preeclampsia and sepsis are the primary causes of ICU admission.

Differential expression of plasma cytokines in sepsis patients and their clinical implications.

Sepsis, which is characterized by acute systemic inflammation and is associated with high rates of morbidity and mortality, presents a significant challenge in health care. Some scholars have found that the sequential organ failure assessment (SOFA) and quick SOFA scores are not ideal for predicting severe sepsis and mortality. Microbial culture takes a long time (2-3 d) and provides no information for early diagnosis and treatment. Therefore, new diagnostic methods for sepsis need to be explored. To assess cytokine levels in the plasma of sepsis patients and identify potential biomarkers for diagnosing sepsis. Ten sepsis patients admitted to the emergency department within 24 h of onset were enrolled as the observation group, whereas ten noninfected patients served as the control group. Of the 10 noninfected patients, 9 hypertension combined with cerebral infarction, 1 patients with vertiginous syndrome. Plasma Cytokines were measured using the Bio-Plex Pro™ Human Chemokine Panel 40-plex. Differentially expressed cytokines in plasma of sepsis and nonsepsis patients were analyzed using Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Interleukin (IL)-16, granulocyte-macrophage granulocyte-macrophage colony-stimulating factor (GM-CSF), CX3CL1, CXCL9, CXCL16, CCL25, and CCL23 plasma levels were significantly increased in sepsis patients. GO analysis revealed that these cytokines were mainly associated with cellular structures such as intermediates, nuclear plaques, adhesion plaques, lateral plasma membranes, and cell matrix junctions. These genes were involved in various molecular functions, such as cytokine activity, receptor ligand activity, and signal receptor activator activity, contributing to various biological functions, such as leukocyte chemotaxis, migration, and chemotaxis. KEGG analysis indicated involvement in cytokine cytokine receptor interactions, chemokine signaling pathways, virus-protein interactions with cytokines and cytokine receptors, and the tumor necrosis factor signaling pathway. Elevated serum levels of IL-16, GM-CSF, CX3CL1, CXCL9, CXCL16, CCL25, and CCL23 in sepsis patients suggest their potential as diagnostic biomarkers for sepsis.

CHEMICAL MODIFICATION AND BIOLOGICAL ACTIVITY OF ALGINATE-BASED HYDROGELS

In recent years, the problem of wound infection has risen dramatically. Infectious complications of surgical wounds have increased significantly, often leading to severe sepsis. Gram-negative bacteria and microorganisms, which are immune to virtually all currently available antimicrobials, are the main culprits. In this regard, the development and implementation of innovative drugs and wound dressings, purulent and chronic wound treatment methods is an urgent problem of many domestic and foreign researchers. Brown algae are extracted using an alkaline solution to produce the ionic polysaccharide sodium alginate. It still holds one of the top positions among water-soluble polymers of natural origin as a result of various highly useful practical characteristics. Based on alginate hydrogels, it is possible to create new materials for biotechnological, pharmaceutical and medical purposes, as they have high moisture retention capacity, non-toxicity and self-decomposing ability. After reviewing the literature, we concluded that cefepime is a new antibiotic researched for wound dressing using IV generation cephalosporins as an antibacterial agent. It is highly resistant to hydrolysis by most beta-lactamases and quickly penetrates the cells of gram-negative bacteria. Inside the bacterial cell, it targets penicillin-binding proteins. To obtain new derivatives of sodium alginate with special properties, a chemical method, in particular, thiolene reactions, was used. It should be noted that click chemistry refers to a set of chemical reactions for the rapid and reliable synthesis of compounds by the uniform addition of individual components. Thiolene reactions offer significant advantages, includingversatile reaction conditions (including radical reactions and catalytic processes) and the ability to use a wide range of substrates with different unsaturated bonds such as acrylates, methacrylates and ethers. To monitor the rate and efficiency of UV activation, we used a sol-gel assay technique that allowed us to quantify insoluble (spatially cross-linked) and soluble polymers. After UV activation, samples with different ratios of thiol derivative (S-H bond) showed low viscosity, indicating the predominant degradation of polymer molecules in these systems. Since alginate-polymer derivatives primarily exhibit deconstructive behavior, the dominant process in alginate molecules is the breaking of bonds rather than their formation. The size of the gel fraction reflects the efficiency of polymer cross-linking, which in turn affects the efficiency of immobilization of the drug in the hydrogel matrix and its release rate. This study presents an experimental characterization of photocrosslinked hydrogels aimed at evaluating and elucidating the physicochemical and biological properties of the antibiotic cefepime in an alginate polymer. The obtained kinetic parameters of the swelling-dissolving process show that the synthesized alginate hydrogel is capable of providing a diffused and prolonged release of drugs. In addition, the synthesized hydrogel effectively delivers cefepime to the tested bacterial strains, showing high antibacterial activity without toxicity. However, further in vivo studies are needed to evaluate the fate and toxicity of the alginate-based hydrogel before definitive conclusions can be drawn regarding the usefulness of the synthesized drugs. These preliminary results can be the basis for the development of medical products.

IMPACT OF ABCC8 AND TRPM4 GENETIC VARIATION IN CENTRAL NERVOUS SYSTEM DYSFUNCTION ASSOCIATED WITH PEDIATRIC SEPSIS.

Background: Sepsis-associated brain injury is associated with deterioration of mental status, persistent cognitive impairment, and morbidity. The SUR1/TRPM4 channel is a nonselective cation channel that is transcriptionally upregulated in the central nervous system with injury, allowing sodium influx, depolarization, cellular swelling, and secondary injury. We hypothesized that genetic variation in ABCC8 (SUR1 gene) and TRPM4 would associate with central nervous system dysfunction in severe pediatric sepsis. Methods: 326 children with severe sepsis underwent whole exome sequencing in an observational cohort. We compared children with and without central nervous system dysfunction (Glasgow Coma Scale <12) to assess for associations with clinical characteristics and pooled rare variants in ABCC8 and TRPM4. Sites of variation were mapped onto protein structure and assessed for phenotypic impact. Results: Pooled rare variants in either ABCC8 or TRPM4 associated with decreased odds of central nervous system dysfunction in severe pediatric sepsis (OR 0.14, 95% CI 0.003-0.87), P = 0.025). This association persisted following adjustment for race, organ failure, viral infection, and continuous renal replacement therapy (aOR 0.11, 95% CI 0.01-0.59, P = 0.038). Structural mapping showed that rare variants concentrated in the nucleotide-binding domains of ABCC8 and N-terminal melastatin homology region of TRPM4 . Conclusion : This study suggests a role for the ABCC8/TRPM4 channel in central nervous system dysfunction in severe pediatric sepsis. Although exploratory, the lack of therapies to prevent or mitigate central nervous system dysfunction in pediatric sepsis warrants further studies to clarify the mechanism and confirm the potential protective effect of these rare ABCC8/TRPM4 variants.

RAB13 regulates macrophage polarization in sepsis

To select the core target (RAB13) in sepsis patients’ peripheral blood and investigate its molecular functions and possible mechanisms. The peripheral blood of sepsis patients (n = 21) and healthy individuals (n = 9) within 24 h after admission were collected for RNA-seq, and differential gene screening was performed by iDEP online analysis software (P < 0.01; log2FC ≥ 2) and enrichment analysis, the potential core target RAB13 was screened out. The association between RAB13 expression and sepsis severity was explored using multiple datasets in the GEO database, and survival analysis was conducted. Subsequently, peripheral blood mononuclear cells (PBMCs) from sepsis and control groups were isolated, and 10 × single-cell sequencing was used to identify the main RAB13-expressing cell types. Finally, LPS was used to stimulate THP1 cells to construct a sepsis model to explore the function and possible mechanism of RAB13. We found that RAB13 was a potential core target, and RAB13 expression level was positively associated with sepsis severity and negatively correlated with survival based on multiple public datasets. A single-cell sequencing indicated that RAB13 is predominantly localized in monocytes. Cell experiments validated that RAB13 is highly expressed in sepsis, and the knockdown of RAB13 promotes the polarization of macrophages towards the M2 phenotype. This mechanism may be associated with the ECM-receptor interaction signaling pathway. The upregulation of RAB13 in sepsis patients promotes the polarization of M2-like macrophages and correlates positively with the severity of sepsis.

Understanding, assessing and treating immune, endothelial and haemostasis dysfunctions in bacterial sepsis.

The interplay between the immune system, coagulation, and endothelium is critical in regulating the host response to infection. However, in sepsis and other critical illnesses, a dysregulated immune response can lead to excessive alterations in these mechanisms, resulting in coagulopathy, endothelial dysfunction, and multi-organ dysfunction. This review aims to provide a comprehensive analysis of the pathophysiological mechanisms that govern the complex interplay between immune dysfunction, endothelial dysfunction, and coagulation in sepsis. It emphasises clinical significance, evaluation methods, and potential therapeutic interventions. Understanding these mechanisms is essential for developing effective treatments that can modulate the immune response, mitigate thrombosis, restore endothelial function, and ultimately improve patient survival.

Wandering Spleen Complicated by Thrombocytopenia, Acute Appendicitis, and Sepsis: A Case Report and Literature Review

Wandering spleen (WS) is a rare condition often linked with torsion or infarction, but its association with Bochdalek hernia, acute appendicitis, and thrombocytopenia is exceptionally rare. We present a case of a nine-year-old girl who was admitted with acute abdominal pain, later diagnosed with WS, Bochdalek hernia, and acute appendicitis. A literature search was performed on PubMed and Google Scholar on 30 May 2024 with keywords including “Wandering spleen” and (“Bochdalek Hernia” OR “Sepsis” OR “Acute Appendicitis” OR “Thrombocytopenia”). The management was complicated by severe thrombocytopenia and post-operative sepsis, with Klebsiella pneumoniae as the causative agent. Imaging revealed an abnormally located spleen and significant splenic enlargement over time. The patient’s condition was managed non-operatively concerning the WS, avoiding splenectomy due to the risks of post-splenectomy sepsis. Instead, laparotomy was performed to address the appendicitis and diaphragmatic hernia. The patient experienced post-operative complications, including a seizure and persistent fever, which resolved with appropriate antibiotic therapy. This case underscores the complexity of managing WS with concurrent severe conditions, highlighting the importance of individualised treatment strategies. It also emphasises the need for further studies to explore optimal treatment modalities for such rare and complex presentations. This case serves as an educational example in clinical settings, demonstrating the challenges and considerations when treating multiple rare pathologies simultaneously.

Serum cytokine panels in pediatric clinical practice

BackgroundCytokines are soluble signaling proteins that regulate inflammation and coordinate immune responses. Serum cytokine assays are increasingly used in medical practice, yet our understanding of cytokines as biomarkers for disease remains limited. ObjectivesWe aimed to analyze real-world single center usage of a multiplexed cytokine panel, correlate its results with diagnosis and severity, and explore its utility in pediatric practice. MethodsA multiplexed cytokine panel, able to return same-day results, was implemented in April 2020 at our institution and its performance was validated for clinical use. Coded patient data were collected using a REDCap database, and correlations between cytokine levels and outcomes of interest were analyzed retrospectively. ResultsCytokine levels correlate with acuity of care, with patients admitted to the pediatric intensive care unit (PICU) having the highest cytokine values. Patients with familial HLH (fHLH) showed prominent peaks in IFNγ, IL-10, and TNF, while patients with sepsis exhibited high IL-6 and IL-8 with relatively modest IFNγ, and cytokine release syndrome (CRS) post-CAR T cell therapy often demonstrated pan-panel positivity at peak levels, with a similar pattern as that of fHLH. A ratio of [IFNγ]+[IL-10]/[IL-6]+[IL-8] levels was able to distinguish fHLH and CRS from severe sepsis. ConclusionsCytokine levels correlate with severity of illness and can help differentiate between syndromes that present similarly, including fHLH and CRS compared to sepsis. Cytokine panels can be used as biomarkers to inform diagnosis and management decisions, but significant work remains to dissect complex clinical patterns of disease.

Clinical Characteristics of Candidemia Due to Candida parapsilosis with Serial Episodes: Insights from 5-Year Data Collection at a Tertiary Hospital in Korea.

Blood isolates of the C. parapsilosis complex were collected from February 2019 to January 2023 at a tertiary Korean hospital. Species identification was performed using Vitek 2 or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antifungal susceptibility testing was performed using the Sensititre YeastOne® system. Clinical information was collected, and characteristics were analyzed according to single or serial isolates. A total of 586 blood isolates of the C. parapsilosis complex were recovered from 68 candidemia patients during the study period. Of them, only the first isolate per patient was investigated. The only two isolates were resistant to fluconazole and no isolate was resistant to echinocandins, amphotericin B, or 5-FC. A single episode of candidemia occurred in 35 patients, while serial episodes occurred in 33 patients. Underlying liver diseases, use of vasopressors, ICU admission, severe sepsis, and CVC use were more frequent in patients with serial episodes. There was no significant difference in the median MIC values of antifungal agents or the use of azoles or amphotericin B between single and serial episodes. However, patients with serial episodes more frequently received echinocandin therapy. Overall, there was no significant difference in the 30-day mortality rate between patients with single and serial episodes. Our data indicate that several factors related to the underlying conditions of the patients are associated with C. parapsilosis candidemia with serial episodes, rather than the characteristics of Candida itself.

Venetoclax plus decitabine as a bridge to allogeneic haematopoietic stem-cell transplantation in older patients with acute myeloid leukaemia (VEN-DEC GITMO): final report of a multicentre, single-arm, phase 2 trial

Access to allogeneic haematopoietic stem-cell transplantation (HSCT) remains challenging for older patients (aged >60 years) with acute myeloid leukaemia. We aimed to evaluate the efficacy of venetoclax plus decitabine as first-line therapy and bridge to transplantation in this patient population. This multicentre, single-arm, phase 2 trial was conducted in 20 Gruppo Italiano Trapianto Midollo Osseo (GITMO) centres in Italy. Patients aged ≥60 and <75 years, with newly diagnosed acute myeloid leukaemia categorised as intermediate or high risk according to 2016 WHO and 2017 European LeukemiaNet, an ECOG performance status of less than 2, and considered fit for allogeneic HSCT were included. Patients received oral venetoclax with a 3-day ramp-up: 100 mg on day 1, 200 mg on day 2, and 400 mg once per day from day 3 of cycle one, and then every 28 days of each cycle (two to four in total). Decitabine was administered intravenously at a dose of 20 mg/m2 from days 1 to 5 every 28 days. At cycle one, patients were admitted to hospital for a minimum of 24 h, whereas subsequent cycles could be administered on an outpatient basis. Two additional cycles were allowed while waiting for allogeneic HSCT or for those with no response or partial response after cycle two. The primary endpoint was the proportion of patients who had allogeneic HSCT performed during first complete remission, assessed in all patients who received at least one dose of the study medication. This study was registered with ClinicalTrials.gov (NCT04476199, ongoing) and EudraCT (2020-002297-26). Between June 1, 2021, and Dec 30, 2022, 93 patients were enrolled and started venetoclax plus decitabine induction (44 [47%] at intermediate risk and 49 [53%] at high risk). The median age was 68·5 (IQR 60·3-74·7). All 93 participants were White, of whom 43 (46%) were female and 50 (54%) were male. The median follow-up was 236 days (IQR 121-506). 64 (69%) of 93 patients reached complete remission and 53 (57%) underwent allogeneic HSCT in complete remission. 53 (83%) of 64 with a complete remission underwent allogeneic HSCT. Five (8%) of 64 patients in complete remission relapsed before transplantation and four died as a consequence. Adverse events (grade ≥3) occurred in 49 (53%) of 93 patients. The most common adverse events were infections (including pneumonia, bacterial sepsis, and SARS-CoV-2 causing seven deaths among 28 [57%] of 49 patients), neutropenia (17 [35%]), thrombocytopenia (two [4%], including one fatal CNS bleeding), and cardiac events (four [8%], including one fatal heart failure). No treatment-related deaths were observed. Venetoclax plus decitabine induction can significantly enhance the feasibility of allogeneic HSCT in older patients with acute myeloid leukaemia who are deemed fit for transplantation. AbbVie and Johnson & Johnson.

Value of the biomarker soluble tyrosine kinase 1 type fms (sFLT-1) in the diagnosis and prognosis of sepsis: a systematic review

IntroductionThe present systematic review analyses the role of soluble fms-like tyrosine kinase-1 (sFLT-1) as an indirect biomarCker of endothelial dysfunction in sepsis or septic shock from articles published in Pubmed between 2010 and March 2022. Materials and methodsA systematic review of studies studying sFLT-1 monitoring in intensive care units in adults with sepsis or septic shock vs. controls for sepsis diagnosis and prognosis has been carried out (PROSPERO CRD42023412929 Registry). ResultsThe endothelial dysfunction of sepsis is one of the keys to the development of the disease. VEGF binds to sFlt-1 acting as a competitive inhibitor of VEGF signalling in endothelial cells and thus neutralizes its pro-inflammatory effects. Endothelial dysfunction is reflected in increased sFLT-1 levels. High values of sFLT-1 were used for the differential diagnosis of sepsis versus other inflammatory pathologies, septic shock versus other types of shock, were elevated over time, estimation of disease prognosis, correlation with sepsis severity, organ dysfunction, and mortality prediction. ConclusionsIt is evident that sepsis is based on endothelial dysfunction. sFLT-1 is one of the main biomarkers of microvascular alteration and is a predictive diagnostic and prognostic biomarker.

Cefotaxime Versus Ceftriaxone: A Comprehensive Comparative Review.

Cefotaxime and ceftriaxone are two prominent third-generation cephalosporin antibiotics, which are a class of antimicrobial agents with overlapping antibacterial spectra and therapeutic indications, commonly used in treating severe bacterial infections, including meningitis, sepsis, and respiratory tract infections. Despite their shared antibacterial coverage, these antibiotics differ significantly in their pharmacokinetic characteristics such as half-life, protein binding, and tissue penetration. This comprehensive review systematically compares the pharmacokinetic profiles, pharmacological attributes, clinical efficacy, and safety profiles of cefotaxime and ceftriaxone. It further highlights the importance of understanding the nuanced differences between cefotaxime and ceftriaxone, particularly in clinical settings such as intensive care units or during pediatric treatment, where rapid bactericidal action or prolonged drug activity might influence therapeutic outcomes. While their overlapping spectrums offer versatility, clinicians should consider these distinct pharmacokinetic attributes and associated clinical outcomes to guide optimal antibiotic selection.

Interferon-responsive neutrophils and macrophages extricate SARS-CoV-2 Omicron critical patients from the nasty fate of sepsis.

The SARS-CoV-2 Omicron variant is characterized by its high transmissibility, which has caused a worldwide epidemiological event. Yet, it turns ominous once the disease progression degenerates into severe pneumonia and sepsis, presenting a horrendous lethality. To elucidate the alveolar immune or inflammatory landscapes of Omicron critical-ill patients, we performed single-cell RNA-sequencing (scRNA-seq) of bronchoalveolar lavage fluid (BALF) from the patients with critical pneumonia caused by Omicron infection, and analyzed the correlation between the clinical severity scores and different immune cell subpopulations. In the BALF of Omicron critical patients, the alveolar violent myeloid inflammatory environment was determined. ISG15+ neutrophils and CXCL10+ macrophages, both expressed the interferon-stimulated genes (ISGs), were negatively correlated with clinical pulmonary infection score, while septic CST7+ neutrophils and inflammatory VCAN+ macrophages were positively correlated with sequential organ failure assessment. The percentages of ISG15+ neutrophils were associated with more protective alveolar epithelial cells, and may reshape CD4+ T cells to the exhaustive phenotype, thus preventing immune injuries. The CXCL10+ macrophages may promote plasmablast/plasma cell survival and activation as well as the production of specific antibodies. As compared to the previous BALF scRNA-seq data from SARS-CoV-2 wild-type/Alpha critical patients, the subsets of neutrophils and macrophages with pro-inflammatory and immunoregulatory features presented obvious distinctions, suggesting an immune disparity in Omicron variants. Overall, this study provides a BALF single-cell atlas of Omicron critical patients, and suggests that alveolar interferon-responsive neutrophils and macrophages may extricate SARS-CoV-2 Omicron critical patients from the nasty fate of sepsis.

Review on the Role of Mitochondrial Dysfunction in Septic Encephalopathy.

Septic Encephalopathy (SE) is a frequent and severe complication of sepsis, characterized by a range of neurocognitive impairments from mild confusion to deep coma. The underlying pathophysiology of SE involves systemic inflammation, neuroinflammation, blood-brain barrier (BBB) disruption, and mitochondrial dysfunction. Among these factors, mitochondrial dysfunction plays a pivotal role, contributing to impaired ATP production, increased reactive oxygen species (ROS) generation, and activation of apoptotic pathways, all of which exacerbate neuronal damage and cognitive deficits. Diagnosis of SE relies on clinical evaluation, neuroimaging, electroencephalography (EEG), and laboratory tests, though specific diagnostic markers are still lacking. Epidemiological data show SE is prevalent in intensive care unit (ICU) patients, especially those with severe sepsis or septic shock, with incidence rates varying widely depending on the population and diagnostic criteria used. Recent research highlights the importance of mitochondrial dynamics, including biogenesis, fission, and fusion, in the development of SE. Mitophagy, a selective form of autophagy that degrades damaged mitochondria, plays a critical role in maintaining mitochondrial health and protecting against dysfunction. Targeting mitochondrial pathways and enhancing mitophagy offers a promising therapeutic strategy to mitigate the effects of SE, reduce oxidative stress, prevent apoptosis, and support the resolution of neuroinflammation. Further research is essential to elucidate the mechanisms of mitochondrial dysfunction and mitophagy in SE and develop effective interventions to improve patient outcomes.

Severe sepsis induced by zoledronic acid: A case report.

Zoledronic acid is one of the most commonly used intravenous, highly potent amino diphosphonate salts worldwide and is commonly used in patients with primary or secondary osteoporosis, most of whom are well tolerated. There are currently no reports of severe sepsis induced by zoledronic acid. Here we present the first case of severe sepsis induced by zoledronic acid. We reviewed the literature and found that there is currently a lack of reports on severe sepsis induced by zoledronic acid or other diphosphonates. A 58-year-old woman with severe osteoporosis and Behcet disease developed severe sepsis after treatment with zoledronic acid. Sepsis, septic shock, acute kidney injury, intestinal infection, Behcet disease. The patient was given intensive care immediately after admission, and massive fluid infusion to expand blood volume could not maintain normal blood pressure. Metaraminol was added to maintain circulatory stability, piperacillin-tazobactam was used to strengthen anti-infection, and glucocorticoids were used for anti-inflammatory treatment. The patient was discharged with improvement and followed up in the outpatient clinic. The inducing mechanism of zoledronic acid is not clear, but when the patient has immunosuppression, the use of zoledronic acid should be cautious and monitored. In conclusion, severe sepsis induced by zoledronic acid is a rare but serious complication, and physicians should be aware of this adverse event in time to avoid serious consequences.

Opinions of Patients with Sepsis Concerning Selected Elements of Holistic Patient Nursing Care During Hospitalization

Objectives: In this study, we examined the opinions of patients with severe sepsis concerning selected elements of patient nursing care during hospital treatment. Methods: We studied 105 adult patients with severe sepsis who received hospital treatment in Poland. Patients' opinions were examined concerning the engagement of nurses in the nursing process in the bio-psycho-social sphere and health education from the aspect of self-care after discharge from hospital. Results: Patients with sepsis received the highest level of support from nurses regarding making contacts with the family. Approximately one-third of respondents reported deficits in nursing care in the area of meeting the need for security, observation of vital signs, and assistance with feeding. A portion of respondents did not receive information about the possibility of social support after discharge from hospital. Conclusions: It is necessary to improve nursing care of patients with sepsis in the bio-psycho-social sphere, regarding the observation of vital signs and health education, because approximately one-third of patients reported deficits in these areas.

Presepsin Levels in Infection-Free Subjects with Diabetes Mellitus: An Exploratory Study.

Systemic inflammation has been recognized as the cause and consequence of metabolic dysregulation in diabetes mellitus (DM). Presepsin has recently emerged as a promising biomarker for the detection of bacterial infections and sepsis. There is evidence that gut dysbiosis results in the increased circulating concentrations of Gram-negative bacteria lipopolysaccharide, the linkage of presepsin, which in turn promotes insulin resistance and correlates with the risk of diabetic complications. Thus, we hypothesized that presepsin could reflect the magnitude of systemic inflammation and metabolic decompensation in patients with DM even in the absence of infection. In this cross-sectional pilot study, we included 75 infection-free individuals with well-controlled (n = 19) and uncontrolled (n = 23) type 2 diabetes (T2D), well-controlled (n = 10) and uncontrolled (n = 10) type 1 diabetes (T1D), and normoglycemic controls (n = 13). Presepsin levels were compared between the groups and potential associations with demographic, clinical, and laboratory parameters were explored. We observed that the duration of DM was associated with presepsin values (p = 0.008). When the participants were classified into the type of DM groups, the presepsin levels were found to be lower in the patients with T2D compared to those with T1D (p = 0.008). However, significance in that case was driven by the difference between the well-controlled groups. After adjusting for the effects of DM duration, presepsin was significantly lower in the well-controlled T2D group compared to the well-controlled T1D group [1.34 (2.02) vs. 2.22 (4.20) ng/mL, p = 0.01]. Furthermore, we adjusted our findings for various confounders, including age, body mass index, and waist circumference, and found that the difference in the presepsin values between the adequately controlled groups remained significant (p = 0.048). In conclusion, our findings suggest that presepsin could potentially serve as a surrogate marker of inflammation and metabolic control in people with DM.

Exploring the Relationship Between Cannabis Use And COVID-19 Outcomes.

Background: Cannabis use is becoming increasingly prevalent worldwide, yet the full spectrum of its effects largely remain unknown. Although cannabis have immunomodulatory properties, there remains a significant gap in our understanding of the potential impact of marijuana use on COVID-19 outcomes. The purpose of this study is to evaluate the effect of chronic cannabis use on severe COVID-19. Materials and Methods: National Inpatient Sample Database was used to sample individuals admitted with the diagnosis of COVID-19. Patients were divided into two groups based on cannabis use. Baseline demographics and comorbidities were collected using ICD-10 codes. Patients with missing data or age under 18 were excluded. Propensity matching using R was performed to match cannabis users to non-cannabis users 1:1 on age, race, gender, and 17 other comorbidities. The primary outcome was severe COVID-19 infection, defined as a composite of acute respiratory failure, intubation, acute respiratory distress syndrome (ARDS), or severe sepsis with multiorgan failure. Results: Out of 322,214 patients included in the study, 2,603 were cannabis users. Cannabis users were younger and had higher prevalence of tobacco use. On initial analysis, cannabis users had significantly lower rates of severe COVID-19 infection, intubation, ARDS, acute respiratory failure, severe sepsis with multiorgan failure, mortality, and shorter length of hospital stay. After 1:1 matching, cannabis use was associated with lower rates of severe COVID-19 infection, intubation, ARDS, acute respiratory failure, severe sepsis with multiorgan failure, mortality, and shorter length of hospital stay. Conclusion: Cannabis users had better outcomes and mortality compared with non-users. The beneficial effect of cannabis use may be attributed to its immunomodulatory effects.

Diagnosis and Management of Neonatal Bacterial Sepsis: Current Challenges and Future Perspectives.

Sepsis remains the second cause of death among neonates after the pathological consequences of extreme prematurity. In this review we summarized knowledge about pathogens causing early-onset sepsis (EOS) and late-onset sepsis (LOS), the role of perinatal risk factors in determining the EOS risk, and the tools used to reduce unnecessary antibiotics. New molecular assays could improve the accuracy of standard blood cultures, providing the opportunity for a quick and sensitive tool. Different sepsis criteria and biomarkers are available to date, but further research is needed to guide the use of antibiotics according to these tools. Beyond the historical antibiotic regimens in EOS and LOS episodes, antibiotics should be based on the local flora and promptly modulated if specific pathogens are identified. The possibility of an antibiotic lock therapy for central venous catheters should be further investigated. In the near future, artificial intelligence could help us to personalize treatments and reduce the increasing trend of multidrug-resistant bacteria.