Septic Multiple Organ Dysfunction Research Articles

Potential biomarkers used for risk estimation of pediatric sepsis-associated organ dysfunction and immune dysregulation.

Pediatric sepsis is a serious issue globally and is a significant cause of illness and death among infants and children. Refractory septic shock and multiple organ dysfunction syndrome are the primary causes of mortality in children with sepsis. However, there is incomplete understanding of mechanistic insight of sepsis associated organ dysfunction. Biomarkers present during the body's response to infection-related inflammation can be used for screening, diagnosis, risk stratification/prognostication, and/or guidance in treatment decision-making. Research on biomarkers in children with sepsis can provide information about the risk of poor outcomes and sepsis-related organ dysfunction. This review focuses on clinically used biomarkers associated with immune dysregulation and organ dysfunction in pediatric sepsis, which could be useful for developing precision medicine strategies in pediatric sepsis management in the future. IMPACT: Sepsis is a complex syndrome with diverse clinical presentations, where organ dysfunction is a key factor in morbidity and mortality. Early detection of organ complications is vital in sepsis management, and potential biomarkers offer promise for precision medicine in pediatric cases. Well-designed studies are needed to identify phase-specific biomarkers and improve outcomes through more precise management.

Clinical features and genetic analysis of three patients with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome due to variants of FOXP3 gene

To analyze the clinical characteristics of three patients with Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Three patients with IPEX syndrome diagnosed at the Children's Hospital of Fudan University from January 24, 2013 to July 29, 2019 were selected as the study subjects. Their clinical features, laboratory investigations and results of genetic testing were summarized. Treatment and prognosis were also explored. All of the three children had developed the disorder during infancy. One child had initial features including diabetes and diabetic ketoacidosis, whilst the other two had initiated by diarrhea. All patients had gastrointestinal involvement, and one was diagnosed as very early onset inflammatory bowel disease by colonoscopy and biopsy. Two children also had endocrine glands involvement. One child had manifested type 1 diabetes and positivity for thyroglobulin and thyroid peroxidase antibodies, though his thyroid function had remained normal. Another one had hypothyroidism and was treated by levothyroxine. Genetic testing revealed that all children had harbored missense variants of the FOXP3 gene, including c.1222G>A (p.V408M), c.767T>C (p.M256T) and c.1021A>G (p.T341A). The clinical symptoms of one patient were alleviated following allogeneic hematopoietic stem cell transplantation. One patient was stable after treatment with infliximab plus insulin, and one child had died of refractory septic shock and multiple organ dysfunction syndrome at 3 months old. FOXP3 gene variant-associated IPEX syndrome may have very early onset and diverse clinical manifestations. For male patients with infantile onset chronic diarrhea, multiple endocrine or multiple system involvement, genetic testing is recommended, which may facilitate early diagnosis, treatment and genetic counseling.

Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units.

Intensive care units (ICUs) are expert hospital areas that provide treatment and 24 h care for people who are very sick. Sepsis represents a serious, severe condition and it can lead to septic shock and multiple organ dysfunction syndromes and is one of the most common reasons for patients' hospitalization in ICUs. We wanted to explore the prognostic values of interleukin (IL) 33, soluble suppression of tumorigenicity 2 (sST2), IL 27, and galectin 3 in critically-ill patients. We assumed that these parameters in combination or alone could predict mortality in ICU patients. This research represents a clinical non-randomized prospective study, performed at the Medical Military Academy, a tertiary care hospital in Belgrade, Serbia. The patients were divided in four groups: patients with sepsis (peritonitis, pancreatitis, trauma) and patients without sepsis (trauma). Total number of patients enrolled in the study was 151 and average years of patients were 56.48. The values greater than the cut-off were the predictors of mortality. The IL-33, IL-27 as well as galectin-3 can successfully predict the outcome of critically-ill patients in ICUs. The sST2, cannot predict death in critically-ill patients as a single prognostic factor. However, the combination of at least two biomarkers: IL-33, sST2, IL-27, and galectin-3, gives very significant results in predicting the outcome in patients admitted to ICUs.

Traumatic degloving injuries: a prospective study to assess injury patterns, management, and outcomes at a single center in northern India

Purpose: This study investigated the epidemiology, management, outcomes, and postoperative disabilities of degloving soft tissue injuries (DSTIs) treated at a tertiary care center in northern India.Methods: A prospective study of patients with DSTIs was conducted over 15 months. The type of degloving injury, the mechanism of injury, and any associated injuries were analyzed using the World Health Organization Disability Assessment Schedule (WHODAS) 2.0 along with the management, outcomes, and disabilities at a 3-month follow-up.Results: Among 75 patients with DSTIs, the average age was 27.5 years, 80.0% were male, and 76.0% had been injured in traffic accidents. The majority (93.3%) were open degloving injuries. Lower limbs were affected most often (62.7%), followed by upper limbs (32.0%). Fractures were the most commonly associated injuries (72.0%). Most patients required multiple procedures, including secondary debridement (41.3%), split skin grafting (80.0%), flap coverage (12.0%), or vacuum-assisted closure (24.0%), while five patients underwent conservative management for closed degloving injuries. Postoperative complications included surgical site infections (14.7%) and skin necrosis (10.7%). Two patients died due to septic shock and multiple organ dysfunction syndrome. The mean length of hospital stay was 11.5±8.1 days, with injuries affecting the lower limbs and perineum requiring longer hospital stays. The mean WHODAS 2.0 disability score at 3 months was 19. Most patients had mild disabilities. Time away from work depended largely upon the site and severity of the injury. Approximately 75% of patients resumed their previous job or study, 14% changed their job, and 8% stopped working completely due to residual disability.Conclusions: Closed degloving injuries may be missed in the primary survey, necessitating a high index of suspicion, thorough clinical examination, and protocol-based management. Primary preventive strategies (e.g., road safety protocols, preplacement training, and proper protective equipment in industries) are also needed to reduce the incidence of these injuries.

USP10 regulates macrophage inflammation responses via stabilizing NEMO in LPS-induced sepsis.

Sepsis is a systemic inflammatory response syndrome characterized by persistent inflammation and immunosuppression, leading to septic shock and multiple organ dysfunctions. Ubiquitin-specific peptidase 10 (USP10), a deubiquitinase enzyme, plays a vital role in cancer and arterial restenosis, but its involvement in sepsis is unknown. In this study, we investigated the significance of USP10 in lipopolysaccharide (LPS)-stimulated macrophages and its biological roles in LPS-induced sepsis. Lipopolysaccharides (LPS) were used to establish sepsis models in vivo and in vitro. We use western blot to identify USP10 expression in macrophages. Spautin-1 and USP10-siRNA were utilized for USP10 inhibition. ELISA assays were used to assess for TNF-α and IL-6 in vitro and in vivo. Nuclear and cytoplasmic protein extraction and Confocal microscopy were applied to verify the translocation of NF-κB. Mechanically, co-immunoprecipitation and rescue experiments were used to validate the regulation of USP10 and NEMO. In macrophages, we found that LPS induced USP10 upregulation. The inhibition or knockdown of USP10 reduced the pro-inflammatory cytokines TNF-α and IL-6 and suppressed LPS-induced NF-κB activation by regulating the translocation of NF-κB. Furthermore, we found that NEMO, the regulatory subunit NF-κB essential modulator, was essential for the regulation of LPS-induced inflammation by USP10 in macrophages. NEMO protein evidently interacted with USP10, whereby USP10 inhibition accelerated the degradation of NEMO. Suppressing USP10 significantly attenuated inflammatory responses and improved the survival rate in LPS-induced sepsis mice. Overall, USP10 was shown to regulate inflammatory responses by stabilizing the NEMO protein, which may be a potential therapeutic target for sepsis-induced lung injury.

Coxiella burnetii and Bartonella Endocarditis Diagnosed by Metagenomic Next-Generation Sequencing

(1) Background: Culture-negative endocarditis is challenging to diagnose. Here, we retrospectively identified 23 cases of Coxiella burnetii and Bartonella endocarditis by metagenomic next-generation sequencing. (2) Methods: Twenty-three patients with culture-negative endocarditis were retrospectively enrolled from Guangdong Provincial People's Hospital (n = 23) between April 2019 and December 2021. Metagenomic next-generation sequencing was performed on blood (n = 22) and excised cardiac valvular tissue samples (n = 22) for etiological identification, and Sanger sequencing was performed for pathogenic diagnostic verification. The demographic and clinical data of the 23 patients were obtained from hospital electronic health records. (3) Results: A total of 23 male patients (median age, 56 years (interquartile range, 16)) with culture-negative endocarditis were diagnosed with Coxiella burnetii (n = 21) or Bartonella (n = 2) species infection by metagenomic next-generation sequencing. All patients underwent cardiac surgery. The resected tissue exhibited both a significantly higher number of unique suspected pathogen read-pairs and more unique pathogen read-pairs than the blood specimens. The results of Sanger sequencing tests on all remaining tissue and blood specimens were positive. Oral doxycycline was added to the antibiotic regimen for at least 1.5 years according to etiology. A total of 21 patients (91%) were discharged, and 20 patients were healthy at the 21-month (interquartile range, 15) follow-up visit. One patient exhibited endocarditis relapse with the same pathogen from inadequate antibiotic administration. The last 2 patients (9%) developed septic shock and multiple organ dysfunction syndrome postoperatively and died shortly after discharge. (4) Conclusions: CNE caused by C. burnetii and Bartonella species is challenging to diagnose and exhibits poor outcome due to delayed treatment. In response, mNGS, characterized by high sensitivity and rapid results, is an effective alternative for the etiological identification of C. burnetii and Bartonella endocarditis.

Mesenchymal Stem Cells Role in COVID-19 Myocardial Injury

Coronavirus Disease-19 (COVID-19) has become a global pandemic that affected the lives of billion individuals. The clinical spectrum of the disease varies from asymptomatic form to severe manifestation in term of acute respiratory distress syndrome (ARDS), shock and septic shock and multiple organ dysfunction syndrome (MODS). Clinical studies have also reported an association between COVID-19 and cardiovascular manifestation, such as myocardial injury, arrhythmias, acute coronary syndrome (ACS) and thromboembolism. Myocardial injury has been reported frequently and is associated with high mortality. The currently approved strategies for COVID-19 are supportive rather than curative treatment. Cell-based approaches, primarily using mesenchymal stem cell (MSC) has demonstrated safety and possible efficacy as an adjuvant therapy in COVID-19 patient. Mesenchymal stem cells have shown important role in the therapy of cardiovascular disease due to their prominent features including their ability to differentiate into cardiovascular cells, immunomodulatory properties, antifibrotic activity and ability to undergo neovasculogenic.

Septic Shock And Multiple Organ Dysfunction Syndrome: A Observational Study From Amazon Region

Objectives: To evaluate the risk factors and mortality associated with septic shock and multiple organ dysfunction syndrome (MODS), and to examine associations with unfavorable outcomes among pediatric patients from the Brazilian Amazon. Design: A matched nested case-control, observational, single-center study was conducted between January 1, 2016, and December 31, 2019. Patients: All children admitted to the pediatric intensive care unit (PICU) with sepsis, as defined in the inclusion criteria, were included. Interventions: The selected cases consisted of patients with septic shock with MODS, while the control group consisted of children who were randomly chosen (1:2 ratio) among patients admitted to the PICU, matched for age and sex. Qualified students collected the data while being “blinded” to the research hypotheses. Measurements and Main Results: There was an association between septic shock with MODS and pH, sodium bicarbonate and base excess, hypernatremia, hypocalcemia, and hyperchloremia. In patients with septic shock with or without MODS, hypocalcemia, hyperchloremia, hypomagnesemia, hypokalemia, and hypophosphatemia were associated with mortality. We also observed an association between acute respiratory distress symptoms, elevated anion gap, and hyperlactatemia in patients with septic shock and non-surviving MODS. Infections by gram-negative organisms, changes in coagulation markers, inadequate nutritional status, pulmonar impairment requiring invasive support, and the presence of acute respiratory distress syndrome were associated with an increased risk of septic shock with MODS and mortality. Conclusions: In our study, septic shock with MODS associated with death affected male infants with previous comorbidities, hospitalized for clinical reasons, and coming from other services. The main factors associated with a higher risk of septic shock with MODS in this study were the origin of outside facilities.

Comparison of acute respiratory distress syndrome in patients with COVID-19 and influenza A (H7N9) virus infection

ObjectivesWe aimed to compared the clinical features of acute respiratory distress syndrome (ARDS) induced by COVID-19 and H7N9 virus infections. MethodsClinical data of 100 patients with COVID-19 and 46 patients with H7N9 were retrospectively analyzed. ResultsElevated inflammatory indices and coagulation disorders were more common in COVID-19-ARDS group than in the H7N9-ARDS group. The median interval from illness onset to ARDS development was shorter in H7N9-ARDS. The PaO2/FiO2 level was lower in H7N9-ARDS, whereas the Sepsis-related Organ Failure Assessment score was higher in COVID-19-ARDS. The proportion of patients with disseminated intravascular coagulation and liver injury in COVID-19-ARDS and H7N9-ARDS was 45.5% versus 3.1% and 28.8% versus 50%, respectively (P <0.05). The mean interval from illness onset to death was shorter in H7N9-ARDS. A total of 59.1% patients with H7N9-ARDS died of refractory hypoxemia compared with 28.9% with COVID-19-ARDS (P = 0.014). Patients with COVID-19-ARDS were more likely to die of septic shock and multiple organ dysfunction compared with H7N9-ARDS (71.2% vs 36.4%, P = 0.005). ConclusionPatients with H7N9 were more susceptible to develop severe ARDS and showed a more acute disease course. COVID-19-ARDS was associated with severe inflammatory response and coagulation dysfunction, whereas liver injury was more common in H7N9-ARDS. The main causes of death between patients with the two diseases were different.

Regulatory T Cells: Angels or Demons in the Pathophysiology of Sepsis?

Sepsis is a syndrome characterized by life-threatening organ dysfunction caused by the dysregulated host response to an infection. Sepsis, especially septic shock and multiple organ dysfunction is a medical emergency associated with high morbidity, high mortality, and prolonged after-effects. Over the past 20 years, regulatory T cells (Tregs) have been a key topic of focus in all stages of sepsis research. Tregs play a controversial role in sepsis based on their heterogeneous characteristics, complex organ/tissue-specific patterns in the host, the multi-dimensional heterogeneous syndrome of sepsis, the different types of pathogenic microbiology, and even different types of laboratory research models and clinical research methods. In the context of sepsis, Tregs may be considered both angels and demons. We propose that the symptoms and signs of sepsis can be attenuated by regulating Tregs. This review summarizes the controversial roles and Treg checkpoints in sepsis.

Outcomes of Heated High Flow Nasal Cannula in Patients With Severe or Life-Threatening COVID-19 at a Military Treatment Facility-A Retrospective Cohort Study.

ABSTRACTIntroductionThe coronavirus-19 (COVID-19) pandemic has forced radical changes in management of healthcare in military treatment facilities (MTFs). Military treatment facilities serve unique patients that have a service connection; thus, research and data on this population are relatively sparse. The purpose of this study was to provide descriptive data on characteristics and outcomes of MTF patients with COVID-19 who are treated with heated high-flow nasal cannula (HHFNC).Materials and MethodsWe performed a single-center retrospective cohort study at the Wright-Patterson Medical Center, a 52-bed hospital in an urban setting. We received approval from our Institutional Review Board. The cohort included patients admitted from June 1, 2020, through May 15, 2021 with severe or life-threatening COVID-19 from a positive severe acute respiratory syndrome–related coronavirus 2 reverse transcription polymerase chain reaction test who were placed on HHFNC during their hospital stay. Severe disease was defined as dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93% without supplemental oxygen, partial pressure of arterial oxygen to fraction of inspired oxygen ratio <300, or lung infiltrates involving >50% of lung fields within 24-48 hours. Life-threatening disease was defined as having septic shock or multiple organ dysfunction or requiring intubation. Patients meeting these criteria were retrieved from a quality improvement cohort that represents a consecutive group of patients with COVID-19 admitted to the Wright-Patterson Medical Center.ResultsOur MTF managed 70 cases of severe or life-threatening COVID-19 from June 1, 2020, to May 15, 2021. Of the 70 cases, 19 (27%) were placed on HHFNC. After initiation of HHFNC, median SpO2/FiO2 was 281.8 and at 24 hours 145.4. Median respiratory rate oxygenation at these times were 10.7 and 9.4, respectively. Fifty percent required mechanical ventilation during hospitalization. Median intensive care unit length of stay was 11 days, with a maximum stay of 39 days. Median hospital length of stay was 12 days, with a maximum of 39 days.ConclusionOur retrospective cohort study characterized and analyzed outcomes observed in a MTF population, with severe or life-threatening COVID-19, who were treated with HHFNC. While the study did not have the power to make concrete conclusions on the optimal form of respiratory support for COVID-19 patients, our data support HHFNC as a reasonable treatment modality despite some notable differences between our cohort and prior studied patient populations.

Necrotizing Soft Tissue Infections in Intensive Care.

Background:Necrotizing soft tissue infections (NSTIs) are typically characterized by extensive soft tissue destruction with systemic signs of toxicity, ranging from sepsis to septic shock. Our aim was to analyze the clinical characteristics, microbiological results, laboratory data, therapies, and outcome of patients with NSTIs admitted to an intensive care unit (ICU).Methods:A monocentric observational study of patients admitted to the ICU of a university hospital between January 2009 and December 2017. The demographic characteristics, comorbidities, clinical features, microbiology and laboratory results, organ dysfunctions, therapies, and outcome were retrospectively analyzed.Results:There were 59 patients and 70% males. The mean age (± SD) was 55 ± 18; type II (monomicrobial) NSTI was present in 36 patients (61%); the most common isolated pathogen was Streptococcus pyogenes in 28 patients (48%). Septic shock was diagnosed in 41 patients (70%). The most common organ dysfunctions were circulatory and renal in 42 (71%) and 38 patients (64%). The mean value (± SD) of serum lactate at admission to the ICU was 4.22 ± 5.42 mmol/l, the median SOFA score and SAPS II were 7 (IQR 4 - 10) and 46 (IQR 30.5 - 53). ICU mortality rate was 25%. Both SOFA score and serum lactate demonstrated a good prognostic value regarding ICU outcome (OR 1.29, 95%CI 1.07-1.57, P < 0.007 and OR 1.53, 95%CI 1.19-1.98, P < 0.001). A cut-off value for serum lactate of 6.55 mmol/L positively predicted mortality with 67% sensitivity and 97% specificity.Conclusion:NSTIs carry a high risk of septic shock and multiple organ dysfunction syndrome and thus are still associated with high mortality. In our study, the value of serum lactate at admission to the ICU correlated well with mortality. This easy-to-measure parameter could play a role in the decision-making process regarding prognosis and continuation of care.

Up-to-date information on polymyxin B-immobilized fiber column direct hemoperfusion for septic shock.

Endotoxin adsorption therapy by polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) has been used for the treatment of septic shock patients. Endotoxin, an outer membrane component of Gram-negative bacteria, plays an important role in the pathogenesis of septic shock. Endotoxin triggers a signaling cascade for leukocytes, macrophage, and endothelial cells to secrete various mediators including cytokines and nitric oxide, leading to septic shock and multiple organ dysfunction syndrome. PMX-DHP directly adsorbed not only endotoxin but also monocytes and anandamide. It reduced blood levels of inflammatory cytokines such as interleukin (IL)-1, IL-6, tumor necrosis factor-alpha and IL-17A, adhesion molecules, plasminogen activator inhibitor 1, and high mobility group box-1. As a result, PMX-DHP increased blood pressure and reduced the dose of vasoactive-inotropic agents. PMX-DHP improved monocyte human leukocyte antigen-DR expression in patients with severe sepsis and septic shock. A post hoc analysis of EUPHRATES (Evaluating the Use of Polymyxin B Hemoperfusion in Randomized Controlled Trial of Adults Treated for Endotoxemia and Septic Shock) trial has shown that PMX-DHP significantly reduced 28-day mortality compared with the control group in septic shock patients with endotoxin activity assay level between 0.60 and 0.89. Longer duration of PMX-DHP may be another strategy to bring out the beneficial effects of PMX-DHP. Further studies are needed to confirm the efficacy of PMX-DHP treatment for septic shock.

Efficacy of alanyl glutamine in nutritional support therapy for patients with sepsis: A protocol for systematic review and meta-analysis.

Background:Sepsis is a systemic inflammatory response caused by infection, which is a common complication after severe infection, trauma, shock, and surgery, and is also an important factor in inducing septic shock and multiple organ dysfunction syndrome (MODS), and has become one of the important causes of death in critically ill patients. Septic patients with gastrointestinal transport function weakened, are prone to malnutrition, resulting in decreased immune function, thereby affecting the therapeutic effect. Clinical practice shows that the nutritional metabolism and immune response of patients with sepsis can be effectively improved by giving alanyl glutamine nutritional support treatment, but there is no evidence of evidence-based medicine. The study carried out in this protocol aims to evaluate the effectiveness of alanyl glutamine in nutritional support therapy for patients with sepsis.Methods:The Cochrane Library, PubMed, Embase, Web of Science, WHO International Clinical Trials Registry Platform, CNKI, CBM, VIP, and Wanfang databases were searched by computer, to retrieve all randomized controlled trials (RCTs) on nutritional support for the treatment of sepsis with alanyl glutamine from the date of database establishment to December 2020. Two researchers independently selected the study, extracted and managed the data. RevMan5.3 software was used to analyze the included literature.Results:This study observed the changes of serum albumin (ALB), prealbumin (PAB), hemoglobin (Hb), C-reactive protein (CRP), immunoglobulin (IgG, IgA, and IgM), APACHE II score before and after treatment to evaluate the efficacy of alanyl glutamine in nutritional support therapy for patients with sepsis.Conclusion:This study will provide reliable evidence for the application of alanyl glutamine in nutritional support therapy for patients with sepsis.OSF Registration number:DOI 10.17605/OSF.IO/VRZPJ.

Research advances on the molecular mechanisms of vascular permeability in sepsis

Sepsis is one of the critical illnesses caused by burns, trauma, shock, infection, and so on. In patients with sepsis, vascular permeability is prone to develop through various pathophysiological mechanisms and thus could result in accumulation of tissue fluid, insufficient intravascular fluid, and finally cause septic shock and multiple organ dysfunction syndrome. Recent studies have shown that various factors and mediators involved in the regulation of vascular permeability in sepsis are expected to become targets for clinical treatment of sepsis. In this paper, we have reviewed the research advances on some molecules which are significantly associated with vascular permeability in sepsis, such as vascular endothelial growth factor, angiopoietin, sphingosine-1-phosphate, heparin-binding protein, and Slit2.

Detection of Infection and Sepsis in Burns.

Background: Infection is the most frequent complication after severe burns and has a propensity to progress into sepsis then septic shock and multiple organ dysfunction syndrome (MODS). Improving outcomes in acute burn care depends on early detection of infection to allow prompt interventions. Diagnosis of sepsis in severe burns is uniquely challenging because otherwise-typical clinical signs are masked by the hypermetabolic state and systemic inflammation induced by the burn itself. For this reason, burns have historically been excluded from high-impact studies on the diagnosis and treatment of sepsis. Methods: This article provides a comprehensive three-fold review of current findings and guidelines pertinent to the early detection of infection and sepsis in severe burns. Results: First, evidence-based detection of the most common infections encountered in the burn intensive care unit is reviewed. Second, we analyze the evolution of the diagnostic criteria for sepsis and the evidence regarding their utility in severe burns. Last, we examine the development of biomarkers, from procalcitonin to molecular genomics, for the detection of sepsis. Conclusions: Although gold standard methods of early detection of sepsis in burn patients have yet to be identified, improved understanding and appropriate application of the available diagnostic criteria and assays are paramount to providing effective care of patients with severe burns.

Progress of nicotinamide in preventing infection and sepsis

Sepsis is a common clinical critical disease, which is one of the main causes of septic shock and multiple organ dysfunction syndrome (MODS). Since traditional clinical interventions are simple and limited, the mortality of sepsis remains high and is also one of the main causes of death of intensive care unit (ICU) patients. Nicotinamide has a wide range of cytoprotective effects. A large number of studies have shown that nicotinamide can play an important role in infection and sepsis by repairing mitochondrial function to restore adenosine triphosphate (ATP) level, inhibiting poly (ADP-ribose) polymerase (PARP) activation, inhibiting proinflammatory mediators and antioxidant damage. This article reviews the pathogenesis of sepsis and the role of nicotinamide in sepsis treatment, aiming to provide references for exploring new therapeutic directions and effective therapeutic measures for sepsis.

Diagnosis of severe scrub typhus infection by next-generation sequencing:a case report

BackgroundScrub typhus is an acute febrile illness, which was caused by Orientia tsutsugamushi and transmitted through the bite of chiggers. The diagnosis of scrub typhus could be missed diagnosis due to the absence of the pathognomonic eschar.Case presentationA 76-year-old man was hospitalized with fever and kidney injury and was diagnosed of hemorrhagic fever with renal syndrome first. However, the situation of the illness deteriorated into refractory septic shock and multiple organ dysfunction rapidly,although the treatment of anti-sepsis was used in 3rd-5th day. Orientia tsutsugamushi was determined to be the causative pathogen by Next-generation sequencing of his plasma sample in 6th day. Then, the patient was treated with doxycycline and azithromycin and recovered quickly.ConclusionsNext-generation sequencing was a new diagnostic technology and could identify scrub typhus in accurately and fast without the pathognomonic eschar.

The prognostic value of serum procalcitonin measurements in critically injured patients: a systematic review

BackgroundMajor trauma is associated with high incidence of septic complications and multiple organ dysfunction (MOD), which markedly influence the outcome of injured patients. Early identification of patients at risk of developing posttraumatic complications is crucial to provide early treatment and improve outcomes. We sought to evaluate the prognostic value of serum procalcitonin (PCT) levels after trauma as related to severity of injury, sepsis, organ dysfunction, and mortality.MethodsWe searched PubMed, MEDLINE, EMBASE, the Cochrane Database, and references of included articles. Two investigators independently identified eligible studies and extracted data. We included original studies that assessed the prognostic value of serum PCT levels in predicting severity of injury, sepsis, organ dysfunction, and mortality among critically injured adult patients.ResultsAmong 2015 citations, 19 studies (17 prospective; 2 retrospective) met inclusion criteria. Methodological quality of included studies was moderate. All studies showed a strong correlation between initial PCT levels and Injury Severity Score (ISS). Twelve out of 16 studies demonstrated significant elevation of initial PCT levels in patients who later developed sepsis after trauma. PCT level appeared a strong predictor of MOD in seven out of nine studies. While two studies did not show association between PCT levels and mortality, four studies demonstrated significant elevation of PCT levels in non-survivors versus survivors. One study reported that the PCT level of ≥ 5 ng/mL was associated with significantly increased mortality (OR 3.65; 95% CI 1.03–12.9; p = 0.04).ConclusionPCT appears promising as a surrogate biomarker for trauma. Initial peak PCT level may be used as an early predictor of sepsis, MOD, and mortality in trauma population.

Puerperal sepsis and multiple organ dysfunctions caused by group A streptococcus

Background: Child fever or puerperal sepsis is a significant cause of maternal morbidity and mortality. It is a preventable maternal postpartum complication.1 Group A streptococcus (GAS) infection remains a significant cause for postpartum sepsis as it causes septic shock and multiple organ dysfunction (MODS). There has been a resurgence of severe puerperal GAS infections over the past two decades, although rare, it must be recognized early and treated aggressively. GAS is a common bacteria causing necrotizing fasciitis (NEF) in our region,2 but it caused NEF in only one postpartum patient which is a rarity.3,4,5 We report a case of puerperal GAS infection-causing NEF where the patient underwent multiple surgical debridements complicated with septic shock and MODS, and had a fairly positive outcome.Case presentation: A 26-year old female presented to the emergency department 5 days postpartum with fever, tachycardia, tachypnea, borderline blood pressure, vaginal discharge, and severe pain in the right leg. Her physical examination revealed reddish discoloration of the right lower leg, which was edematous, warm, and extremely tender. The episiotomy wound looked dirty and infected. She had leukocytosis (29.2 × 103/μL), thrombocytopenia (44 × 103/μL), C-Reactive protein was elevated (322 mg/L), and serum lactic acid was 3.8 mmol/L. Her hepatic and renal parameter were elevated. She had a deranged coagulation profile. Post-partum sepsis was suspected and blood cultures were done. She was started on Tazocin® (Tazobactum+piperacillin), supplemented with oxygen, and resuscitated with intravenous fluids.She was immediately taken for emergency surgical intervention, right leg debridement, and fasciotomy with exploration of the episiotomy wound was performed. Surgical findings were dirty colored fluid collection and loss of facial resistance which corroborated with NEF. Necrotic tissues were sent for histopathology and cultures, and clindamycin was started. Intraoperatively the patient became unstable, requiring double vasopressor (noradrenaline and vasopressin) to maintain the hemodynamics. Postoperatively the patient was kept sedated and ventilated in the intensive care unit (ICU). She required four debridements in the next two days despite which her right leg was not improving. Magnetic resonance imaging showed necrotizing fasciitis of the right thigh and leg. Tissue biopsy confirmed the diagnosis. Her blood and tissues showed growth of group A streptococcus. With family agreement, she underwent above right knee amputation, lateral and medial thigh compartment fasciotomy, and debridement on day five. She was oozing from the fasciotomy wounds and needed resuscitation with blood and blood products. She started to show signs of improvement and was weaned off from vasopressors and ventilator. Hepatic and renal functions improved (Figure 1 and Table 1). She was extubated on day 12, awake, hemodynamically stable, tolerated oral feeding, and was transferred to the surgical ward on day 19. She was discharged home on day 24 and was followed in surgical outpatient clinics.Conclusion: Despite developments in infection control and strict aseptic precautions, GAS puerperal sepsis remains a potentially life-threatening infection especially when they present with rare conditions like NEF in the postpartum period. Early diagnosis, aggressive surgical management, and supportive medical care are important for a positive outcome.