RESUMEN

As a grave and highly lethal clinical challenge, sepsis, along with its consequent multiorgan dysfunction, affects millions of people worldwide. Sepsis is a complex syndrome caused by a dysregulated host response to infection, leading to fatal organ dysfunction. An increasing body of evidence suggests that the pathogenesis of sepsis is both intricate and rapid and involves various cellular responses and signal transductions mediated by post-translational modifications (PTMs). Hence, a comprehensive understanding of the mechanisms and functions of PTMs within regulatory networks is imperative for understanding the pathological processes, diagnosis, progression, and treatment of sepsis. In this review, we provide an exhaustive and comprehensive summary of the relationship between PTMs and sepsis-induced organ dysfunction. Furthermore, we explored the potential applications of PTMs in the treatment of sepsis, offering a forward-looking perspective on the understanding of infectious diseases.

Asunto(s)

Asunto(s)

RESUMEN

Importance: Soluble thrombomodulin is a marker of endotheliopathy, and iloprost may improve endothelial function. In patients with septic shock, high plasma levels of soluble thrombomodulin (>10 ng/mL) have been associated with worse organ dysfunction and mortality. Objective: To assess the effects of treatment with iloprost vs placebo on the severity of organ failure in patients with septic shock and plasma levels of soluble thrombomodulin higher than 10 ng/mL. Design, Setting, and Participants: This investigator-initiated, adaptive, parallel group, stratified, double-blind randomized clinical trial was conducted between November 1, 2019, and July 5, 2022, at 6 hospitals in Denmark. The trial had a maximum sample size of 380, with an interim analysis for futility only at 200 patients with 90 days of follow-up. In total, 279 adults in the intensive care unit (ICU) with septic shock and endotheliopathy were included. Interventions: Patients were randomized 1:1 to masked intravenous infusion of iloprost, 1 ng/kg/min (n = 142), or placebo (n = 137) for 72 hours. Main Outcomes and Measures: The primary outcome was mean daily Sequential Organ Failure Assessment (SOFA) score in the ICU adjusted for trial site and baseline SOFA score for the per-protocol population. SOFA scores for each of the 5 organ systems ranged from 0 to 4, with higher scores indicating more severe dysfunction (maximum score, 20). The secondary outcomes included serious adverse reactions and serious adverse events at 7 days and mortality at 90 days. Results: Of 279 randomized patients, data from 278 were analyzed (median [IQR] age, 69 [58-77] years; 171 (62%) male), 142 in the iloprost group and 136 in the placebo group. The trial was stopped for futility at the planned interim analysis. The mean [IQR] daily SOFA score was 10.6 (6.4-14.8) in the iloprost group and 10.5 (5.9-15.5) in the placebo group (adjusted mean difference, 0.2 [95% CI, -0.8 to 1.2]; P = .70). Mortality at 90 days in the iloprost group was 57% (81 of 142) vs 51% (70 of 136) in the placebo group (adjusted relative risk, 1.12 [95% CI, 0.91-1.40]; P = .33). Serious adverse events occurred in 26 of 142 patients (18%) for the iloprost group vs 20 of 136 patients (15%) for the placebo group (adjusted relative risk, 1.25 [95% CI, 0.73-2.15]; P = .52). Only 1 serious adverse reaction was observed. Conclusions and Relevance: In this randomized clinical trial of adults in the ICU with septic shock and severe endotheliopathy, infusion of iloprost, 1 ng/kg/min, for 72 hours did not reduce mean daily SOFA scores compared with placebo. In a clinical context, administration of iloprost will be unlikely to improve outcome in these patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04123444.

Asunto(s)

RESUMEN

BACKGROUND: Group A Streptococcus causes a variety of human infections, including the life-threatening necrotizing fasciitis, which may be ignored by the patient. From hours to days, the infection may progress from an apparently benign skin lesion, usually mistaken for a spider or insect bite, to a highly lethal disease. We present a case of 57-year-old male with skin lesions on swelling left upper limb. METHODS AND RESULTS: The culture of secretion from epidermis and blood were positive for Group A Streptococcus (GAS), type ß hemolytic streptococcus. Intensive anti-infection therapy was applied. However, the necrosis of the limb deteriorated rapidly. He died from multiple organ failure, streptococcal toxic shock syndrome (STSS) and disseminated intravascular coagulation 13 days later. CONCLUSIONS: Necrotizing fasciitis is a rapidly progressive, destructive bacterial infection. Early recognition is the most important factor for survival.

Asunto(s)

RESUMEN

OBJECTIVES: Treatment of hemorrhagic shock (HS) induced multi-organ injury remains a challenge. Bergapten (BeG) is a bioactive coumarin-derived compound, and previous articles have suggested that BeG may serve as a prospective therapeutic modality for HS. This study was designed to investigate the efficacy of BeG in the treatment of HS and its underlying mechanisms. METHODS: In this research, we established a rat model of HS, following which we assessed the protective effects of BeG on HS induced multi-organ injury. Subsequently, we scrutinized the activation of NLRP3 inflammasomes and pyroptosis in damaged organs. Additionally, we conducted examinations of AMPK and the downstream mitophagy pathway in damaged organs. Finally, we established a hypoxia/reoxygenation (H/R) model in HK-2 cells to simulate the in vitro HS process. Following AMPK inhibition with compound C, we evaluated the levels of mitophagy and cellular pyroptosis in BeG-treated HK-2 cells subjected to H/R. RESULTS: BeG treatment alleviated HS induced multi-organ injury. Subsequent analyses indicated that the therapeutic effects of BeG were related to the attenuation of NLRP3 inflammasome activation and pyroptosis. Additionally, we found BeG treatment stimulated the phosphorylation of AMPK, thereby enhancing mitophagy. Lastly, we found that the inhibition of AMPK in vitro attenuates BeG's enhancement of mitophagy and its suppression of pyroptosis. CONCLUSION: Our research indicates that BeG has the potential to alleviate multi-organ injury induced by HS. The protective effect of BeG is likely associated with its promotion of mitophagy through AMPK activation, thereby inhibiting NLRP3 inflammasome-mediated pyroptosis.

Asunto(s)

RESUMEN

In recent years, gene therapy has been made possible with the success of nucleic acid drugs against sepsis and its related organ dysfunction. Therapeutics based on nucleic acids such as small interfering RNAs (siRNAs), microRNAs (miRNAs), messenger RNAs (mRNAs), and plasmid DNAs (pDNAs) guarantee to treat previously undruggable diseases. The advantage of nucleic acid-based therapy against sepsis lies in the development of nanocarriers, achieving targeted and controlled gene delivery for improved efficacy with minimal adverse effects. Entrapment into nanocarriers also ameliorates the poor cellular uptake of naked nucleic acids. In this study, we discuss the current state of the art in nanoparticles for nucleic acid delivery to treat hyperinflammation and apoptosis associated with sepsis. The optimized design of the nanoparticles through physicochemical property modification and ligand conjugation can target specific organs-such as lung, heart, kidney, and liver-to mitigate multiple sepsis-associated organ injuries. This review highlights the nanomaterials designed for fabricating the anti-sepsis nanosystems, their physicochemical characterization, the mechanisms of nucleic acid-based therapy in working against sepsis, and the potential for promoting the therapeutic efficiency of the nucleic acids. The current investigations associated with nanoparticulate nucleic acid application in sepsis management are summarized in this paper. Noteworthily, the potential application of nanotherapeutic nucleic acids allows for a novel strategy to treat sepsis. Further clinical studies are required to confirm the findings in cell- and animal-based experiments. The capability of large-scale production and reproducibility of nanoparticle products are also critical for commercialization. It is expected that numerous anti-sepsis possibilities will be investigated for nucleic acid-based nanotherapeutics in the future.

Asunto(s)

RESUMEN

There is extensive overlap of clinical features among familial or primary HLH (pHLH), reactive or secondary hemophagocytic lymphohistiocytosis (sHLH) [including macrophage activation syndrome (MAS) related to rheumatic diseases], and hyperferritinemic sepsis-induced multiple organ dysfunction syndrome (MODS); however, the distinctive pathobiology that causes hyperinflammatory process in each condition requires careful considerations for therapeutic decision-making. pHLH is defined by five or more of eight HLH-2004 criteria [1], where genetic impairment of natural killer (NK) cells or CD8+ cytolytic T cells results in interferon gamma (IFN-γ)-induced hyperinflammation regardless of triggering factors. Cytolytic treatments (e.g., etoposide) or anti-IFN-γ monoclonal antibody (emapalumab) has been effectively used to bridge the affected patients to hematopoietic stem cell transplant. Secondary forms of HLH also have normal NK cell number with decreased cytolytic function of varying degrees depending on the underlying and triggering factors. Although etoposide was uniformly used in sHLH/MAS in the past, the treatment strategy in different types of sHLH/MAS is increasingly streamlined to reflect the triggering/predisposing conditions, severity/progression, and comorbidities. Accordingly, in hyperferritinemic sepsis, the combination of hepatobiliary dysfunction (HBD) and disseminated intravascular coagulation (DIC) reflects reticuloendothelial system dysfunction and defines sepsis-associated MAS. It is demonstrated that as the innate immune response to infectious organism prolongs, it results in reduction in T cells and NK cells with subsequent lymphopenia even though normal cytolytic activity continues (Figs. 30.1, 30.2, 30.3, and 30.4). These changes allow free hemoglobin and pathogens to stimulate inflammasome activation in the absence of interferon-γ (IFN-γ) production that often responds to source control, intravenous immunoglobulin (IVIg), plasma exchange, and interleukin 1 receptor antagonist (IL-1Ra), similar to non-EBV, infection-induced HLH.

Asunto(s)

RESUMEN

Disseminated intravascular coagulation (DIC) poses a high mortality risk, yet its exact impact remains contentious. This study investigates DIC's association with mortality in individuals with sepsis, emphasizing multiple organ function. Using data from the Peking University People's Hospital Investigation on Sepsis-Induced Coagulopathy database, we categorized patients into DIC and non-DIC groups based on DIC scores within 24 h of ICU admission (< 5 cutoff). ICU mortality was the main outcome. Initial data comparison preceded logistic regression analysis of mortality factors post-propensity score matching (PSM). Employing mediation analysis estimated direct and indirect associations. Of 549 participants, 131 were in the DIC group, with the remaining 418 in the non-DIC group. Following baseline characteristic presentation, PSM was conducted, revealing significantly higher nonplatelet sequential organ failure assessment (nonplt-SOFA) scores (6.3 ± 2.7 vs 5.0 ± 2.5, P < 0.001) and in-hospital mortality rates (47.3% vs 29.5%, P = 0.003) in the DIC group. A significant correlation between DIC and in-hospital mortality persisted (OR 2.15, 95% CI 1.29-3.59, P = 0.003), with nonplt-SOFA scores (OR 1.16, 95% CI 1.05-1.28, P = 0.004) and hemorrhage (OR 2.33, 95% CI 1.08-5.03, P = 0.032) as predictors. The overall effect size was 0.1786 (95% CI 0.0542-0.2886), comprising a direct effect size of 0.1423 (95% CI 0.0153-0.2551) and an indirect effect size of 0.0363 (95% CI 0.0034-0.0739), with approximately 20.3% of effects mediated. These findings underscore DIC's association with increased mortality risk in patients with sepsis, urging anticoagulation focus over bleeding management, with organ dysfunction assessment recommended for anticoagulant treatment efficacy.

Asunto(s)

RESUMEN

Vitamin K is an essential dietary cofactor required for the synthesis of active forms of vitamin K-dependent procoagulant proteins. Vitamin K deficiency, particularly late-onset deficiency occurring between 1 week and 6 months of age, can cause a life-threatening bleeding disorder. An exclusively breastfed, full-term, 6-week-old infant male presented with severe haemorrhagic shock and multi-system organ failure related to caregiver refusal of intramuscular vitamin K after birth. Coagulation studies were normalised within 8 hours of intramuscular vitamin K administration. An increasing number of caregivers are refusing intramuscular vitamin K which has led to a rise in the incidence of vitamin K deficiency bleeding. Health policy organisations around the world emphasise the benefits of intramuscular vitamin K and risks of refusal, particularly in exclusively breastfed infants who are at higher risk due to low vitamin K levels in breast milk. This case highlights the multi-system severity of this life-threatening yet preventable disorder.

Asunto(s)

RESUMEN

OBJECTIVES: To provide a comprehensive summary of the published data on cause of death in patients with acute respiratory distress syndrome (ARDS). DATA SOURCES: PubMed (January 2015 to April 2024), bibliographies of relevant articles, and ARDS Network and Prevention & Early Treatment of Acute Lung Injury (PETAL) network websites. STUDY SELECTION: Observational studies and clinical trials that reported on cause of death in greater than or equal to 30 patients with ARDS, not obtained from death certificates. Animal studies, case reports, review articles, study protocols, and studies in pediatrics were excluded. DATA EXTRACTION: Causes of death among ARDS patients who died were extracted and tabulated along with other pertinent study characteristics. DATA SYNTHESIS: We identified 15 observational studies (nine non-COVID ARDS, five COVID-related ARDS; one both) and five clinical trials (all non-COVID ARDS). Mutually exclusive prespecified categories were used for recording the cause of death in only eight studies although studies differed in the categories included and their definitions. When multiple organ failure was a predetermined category, it was the most common cause of death recorded (~50% of deaths), followed by respiratory causes with proportions varying from 16% to 42% depending on nomenclature (e.g., refractory hypoxemia, pulmonary causes) and definitions. However, the largest observational study in non-COVID ARDS (964 deaths), did not include multiple organ failure as a predetermined category, and found that pulmonary failure (42%) and cardiac failure (37%) were the most common causes of death. In COVID-related ARDS observational studies, pulmonary reasons were the most reported cause of death (up to 88%). CONCLUSIONS: Few studies have reported cause of death in patients with ARDS. In those that do, cause of death categories and definitions used are heterogeneous. Further research is needed to see whether a more rigorous and unified approach to assigning and reporting cause of death in ARDS would help identify more relevant endpoints for the assessment of targeted treatments in clinical trials.

Asunto(s)

RESUMEN

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis causes a high mortality rate and current treatment focuses on supportive therapies but lacks specific therapeutic targets. Notably, sirtuins (SIRTs) shows potential clinical application in the treatment of sepsis. It has been demonstrated that SIRTs, the nicotinamide adenine dinucleotide+(NAD+)-dependent deacetylases that regulate key signaling pathways in eukaryotes and prokaryotes, are involved in a variety of biological processes. To date, seven mammalian yeast Sir2 homologs have been identified. SIRTs can regulate inflammation, oxidative stress, apoptosis, autophagy, and other pathways that play important roles in sepsis-induced organ dysfunction. However, the existing studies on SIRTs in sepsis are too scattered, and there is no relevant literature to integrate them. This review innovatively summarizes the different mechanisms of SIRTs in sepsis organ dysfunction according to the different systems, and focuses on SIRT agonists, inhibitors, and targeted drugs that have been proved to be effective in the treatment of sepsis, so as to integrate the clinical research and basic research closely. We searched PubMed for all literature related to SIRTs and sepsis since its inception using the following medical subject headings: sirtuins, SIRTs, and sepsis. Data on the mechanisms of SIRTs in sepsis-induced organ damage and their potential as targets for disease treatment were extracted.

Asunto(s)

RESUMEN

Malnutrition is an important risk factor for multiple organ dysfunction syndrome in the elderly (MODSE) and seriously affects the occurrence, progression and prognosis of MODSE. Shenling Baizhu Power (SBP), a classic formula from traditional Chinese medicine (TCM), when integrated with enteral nutrition, has been proven to be an effective clinical strategy for treating the patients of MODSE with malnutrition. This study aimed to investigate the metabolic changes during disease occurrence and SBP treatment, and to discover potential metabolic biomarkers for the diagnosis and efficacy evaluation. An untargeted metabolomics strategy based on UHPLC-Q-Orbitrap-HRMS was performed to reveal the differential serum metabolites between MODSE patients with malnutrition (n=59) and healthy controls (n=33), and those between patients treated with enteral nutrition (n=31) and SBP combined with enteral nutrition (n=28). Significantly different metabolites were identified and mapped onto the network of metabolic pathways to explore the metabolic disorders caused by the disease and the metabolic regulatory mechanism of SBP. Additionally, the area under the curve (AUC) of the potential biomarkers was investigated for predicting the disease and the efficacy of SBP. Sixty differential metabolites were identified between the disease and control groups, which were mainly related to amino acid metabolism, energy metabolism and carbohydrate metabolism. In the same way, 50 differential metabolites associated with SBP treatment were identified, which improved metabolic abnormalities in vivo mainly by regulating the above-mentioned metabolic pathways. Finally, 13 differential metabolites in common were selected as the potential biomarkers and the AUC value of each biomarker was within the range of 0.8-1.0, indicating that these biomarkers had high prediction accuracy for the diagnosis and efficacy evaluation of MODSE with malnutrition. This study demonstrates that serum metabolomics approaches based on the UHPLC-Q-Orbitrap-HRMS platform can be applied as a tool to reveal the metabolic changes induced by MODSE with malnutrition and SBP can play an important role in the clinical application.

Asunto(s)

RESUMEN

INTRODUCTION: Extensive trauma, commonly seen in wounded military Service Members, often leads to a severe sterile inflammation termed systemic inflammatory response syndrome (SIRS), which can progress to multiple organ dysfunction syndrome (MODS) and death. MODS is a serious threat to wounded Service Members, historically causing 10% of all deaths in trauma admissions at a forward deployed combat hospital. The importance of this problem will be exacerbated in large-scale combat operations, in which evacuation will be delayed and care of complex injuries at lower echelons of care may be prolonged. The main goal of this study was to optimize an existing mouse model of lethal SIRS/MODS as a therapeutic screening platform for the evaluation of immunomodulatory drugs. MATERIALS AND METHODS: Male C57BL/6 mice were euthanized, and the bones and muscles were collected and blended into a paste termed tissue-bone matrix (TBX). The TBX at 12.5%-20% relative to body weight of each recipient mouse was implanted into subcutaneous pouches created on the dorsum of anesthetized animals. Mice were observed for clinical scores for up to 48 hours postimplantation and euthanized at the preset point of moribundity. To test effects of anesthetics on TBX-induced mortality, animals received isoflurane or ketamine/xylazine (K/X). In a separate set of studies, mice received TBX followed by intraperitoneal injection with 20 mg/kg or 40 mg/kg Eritoran or a placebo carrier. All Eritoran studies were performed in a blinded fashion. RESULTS: We observed that K/X anesthesia significantly increased the lethality of the implanted TBX in comparison to inhaled anesthetics. Although all the mice anesthetized with isoflurane and implanted with 12.5% TBX survived for 24 hours, 60% of mice anesthetized with K/X were moribund by 24 hours postimplantation. To mimic more closely the timing of lethal SIRS/MODS following polytrauma in human patients, we extended observation to 48 hours. We performed TBX dose-response studies and found that as low as 15%, 17.5%, and 20% TBX caused moribundity/mortality in 50%, 80%, and 100% mice, respectively, over a 48-hour time period. With 17.5% TBX, we tested if moribundity/mortality could be rescued by anti-inflammatory drug Eritoran, a toll-like receptor 4 antagonist. Neither 20 mg/kg nor 40 mg/kg doses of Eritoran were found to be effective in this model. CONCLUSIONS: We optimized a TBX mouse model of SIRS/MODS for the purpose of evaluating novel therapeutic interventions to prevent trauma-related pathophysiologies in wounded Service Members. Negative effects of K/X on lethality of TBX should be further evaluated, particularly in the light of widespread use of ketamine in treatment of pain. By mimicking muscle crush, bone fracture, and necrosis, the TBX model has pleiotropic effects on physiology and immunology that make it uniquely valuable as a screening tool for the evaluation of novel therapeutics against trauma-induced SIRS/MODS.

Asunto(s)

RESUMEN

BACKGROUND: Ulinastatin has been applied in a series of diseases associated with inflammation but its clinical effects remain somewhat elusive. OBJECTIVE: We aimed to investigate the potential effects of ulinastatin on organ failure patients admitted to the intensive care unit (ICU). METHODS: This is a single-center retrospective study on organ failure patients from 2013 to 2019. Patients were divided into two groups according to using ulinastatin or not during hospitalization. Propensity score matching was applied to reduce bias. The outcomes of interest were 28-day all-cause mortality, length of ICU stay, and mechanical ventilation duration. RESULTS: Of the 841 patients who fulfilled the entry criteria, 247 received ulinastatin. A propensity-matched cohort of 608 patients was created. No significant differences in 28-day mortality between the two groups. Sequential organ failure assessment (SOFA) was identified as the independent risk factor associated with mortality. In the subgroup with SOFA ≤ 10, patients received ulinastatin experienced significantly shorter time in ICU (10.0 d [interquartile range, IQR: 7.0∼20.0] vs 15.0 d [IQR: 7.0∼25.0]; p = .004) and on mechanical ventilation (222 h [IQR:114∼349] vs 251 h [IQR: 123∼499]; P = .01), but the 28-day mortality revealed no obvious difference (10.5% vs 9.4%; p = .74). CONCLUSION: Ulinastatin was beneficial in treating patients in ICU with organ failure, mainly by reducing the length of ICU stay and duration of mechanical ventilation.

Asunto(s)

RESUMEN

Cytokine storm syndrome (CSS) is a severe life-threatening condition characterized by a clinical phenotype of overwhelming systemic inflammation, hyperferritinemia, hemodynamic instability, and multiple organ failure (MOF), and, if untreated, it can potentially lead to death. The hallmark of CSS is an uncontrolled and dysfunctional immune response involving the continual activation and expansion of lymphocytes and macrophages, which secrete large amounts of cytokines, causing a cytokine storm. Many clinical features of CSS can be explained by the effects of pro-inflammatory cytokines, such as interferon (IFN)-γ, tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, and IL-18 [1-7]. These cytokines are elevated in most patients with CSS as well as in animal models of CSS [8, 9]. A constellation of symptoms, signs, and laboratory abnormalities occurs that depends on the severity of the syndrome, the underlying predisposing conditions, and the triggering agent.

Asunto(s)

RESUMEN

Casein kinase II (CK2) has recently emerged as a pivotal mediator in the propagation of inflammation across various diseases. Nevertheless, its role in the pathogenesis of sepsis remains unexplored. Here, we investigated the involvement of CK2 in sepsis progression and the potential beneficial effects of silmitasertib, a selective and potent CK2α inhibitor, currently under clinical trials for COVID-19 and cancer. Sepsis was induced by caecal ligation and puncture (CLP) in four-month-old C57BL/6OlaHsd mice. One hour after the CLP/Sham procedure, animals were assigned to receive silmitasertib (50 mg/kg/i.v.) or vehicle. Plasma/organs were collected at 24 h for analysis. A second set of experiments was performed for survival rate over 120 h. Septic mice developed multiorgan failure, including renal dysfunction due to hypoperfusion (reduced renal blood flow) and increased plasma levels of creatinine. Renal derangements were associated with local overactivation of CK2, and downstream activation of the NF-ĸB-iNOS-NO axis, paralleled by a systemic cytokine storm. Interestingly, all markers of injury/inflammation were mitigated following silmitasertib administration. Additionally, when compared to sham-operated mice, sepsis led to vascular hyporesponsiveness due to an aberrant systemic and local release of NO. Silmitasertib restored sepsis-induced vascular abnormalities. Overall, these pharmacological effects of silmitasertib significantly reduced sepsis mortality. Our findings reveal, for the first time, the potential benefits of a selective and potent CK2 inhibitor to counteract sepsis-induced hyperinflammatory storm, vasoplegia, and ultimately prolonging the survival of septic mice, thus suggesting a pivotal role of CK2 in sepsis and silmitasertib as a novel powerful pharmacological tool for drug repurposing in sepsis.

Asunto(s)

RESUMEN

PURPOSE: Cardiac surgery, post-cardiotomy cardiogenic shock (PCCS), and temporary mechanical circulatory support (tMCS) provoke substantial inflammation. We therefore investigated whether a selenium-based, anti-inflammatory strategy would benefit PCCS patients treated with tMCS in a post-hoc analysis of the sustain CSX trial. METHODS: Post-hoc analysis of patients receiving tMCS for PCCS in the Sustain CSX trial, which investigated the effects of high-dose selenium on postoperative organ dysfunction in cardiac surgery patients. PRIMARY OUTCOME: duration of tMCS therapy. SECONDARY OUTCOMES: postoperative organ dysfunction and 30-day mortality. RESULTS: Thirty-nine patients were treated with tMCS for PCCS. There was no difference in the median duration of tMCS between the selenium and the placebo group (3 days [IQR: 1-6] vs. 2 days [IQR: 1-7], p = 0.52). Median dialysis duration was longer in the selenium group (1.5 days [0-21.8] vs. 0 days [0-1.8], p = 0.048). There was no difference in 30-day mortality (53% vs. 41%, OR 1.44, 95% CI 0.32-6.47, p = 0.62). CONCLUSION: In this explorative study, a perioperative high-dose selenium-supplementation did not show beneficial effects on organ dysfunctions and mortality rates in patients with PCCS receiving tMCS.

Asunto(s)

RESUMEN

Infection with the SARS-CoV-2 virus may induce some complications among people who experience mild to moderate respiratory illness and some of them recover without requiring special treatment. Albeit, some individuals become seriously reached risk points and require special medical attention especially older people and people who suffer from chronic diseases. Serum and whole blood samples were collected from confirmed infected persons with SARS CoV-2 by real-time PCR and the control group. All lab. Investigations were performed using Cobas 6000. Significant differences were noted between patients compared to the control group in the Mean ± SD of IL-6 (76.06 ± 7.60 vs 3.61 ± 0.296 pg/ml), Procalcitonin (0.947 ± 0.117 vs 0.061 ± 0.007 ng/ml), CRP (125.3 ± 7.560 vs 4.027 ± 0.251 mg/dl), ALT (154.8 ± 30.47 vs 49.75 ± 2.977 IU/L) and AST (70.83 ± 9.215 vs 27.23 ± 1.767) respectively. While other parameters were also showed significant differences were noted between patients compared to the control group for D-Dimmer, PT, PTT, LDH, Ferritin, WBC, Lymphocyte and Creatinine. The results reached that the effect of SARS CoV-2 and cytokine storm was clear on the body's organs through vital biomarker investigations that were performed in this study.

Asunto(s)

RESUMEN

Sepsis and septic shock are critical medical conditions characterized by a systemic inflammatory response to infection, significantly contributing to global mortality rates. The progression to multiple organ dysfunction syndrome (MODS) represents the most severe complication of sepsis and markedly increases clinical mortality. Central to the pathophysiology of sepsis, endothelial cells play a crucial role in regulating microcirculation and maintaining barrier integrity across various organs and tissues. Recent studies have underscored the pivotal role of endothelial function in the development of sepsis-induced MODS. This review aims to provide a comprehensive overview of the pathophysiology of sepsis-induced MODS, with a specific focus on endothelial dysfunction. It also compiles compelling evidence regarding potential small molecules that could attenuate sepsis and subsequent multi-organ damage by modulating endothelial function. Thus, this review serves as an essential resource for clinical practitioners involved in the diagnosing, managing, and providing intensive care for sepsis and associated multi-organ injuries, emphasizing the importance of targeting endothelial cells to enhance outcomes of the patients.

Asunto(s)

RESUMEN

A 19-year-old male patient with high-risk acute B-cell lymphoblastic leukemia received haploidentical stem cell transplantation. He developed anemia repeatedly and parvovirus B19 nucleic acid was positive in blood plasma. The patient was diagnosed with cold agglutinin syndrome and multiple organ dysfunction including respiratory failure and hepatitis. In the conflict between viral infection and the treatment of cold agglutinin syndrome, we provided supportive treatment, complement inhibitors to control hemolysis, and antiviral therapy. After timely glucocorticoid and immunosuppressant therapy, the patient had achieved a good response.

Asunto(s)