Septic Organ Research Articles

40 Years of Helicobacter pylori: A Revolution in Biomedical Thought

Background: Various microorganisms such as bacteria, virus, and fungi can infect humans and cause not just a simple infection but septic conditions, organ dysfunction, and precancerous conditions or cancer involving various organ systems. After the discovery of the microscope, it was easier to discover and study such microorganisms, as in the case of Helicobacter pylori, a pathogen that was seen in the distant era of the nineteenth century but without being recognized as such. It took 100 years to later discover the pathogenesis and the cancer that this bacterium can cause. Since it was discovered, until today, there has been a continuous search for the understanding of its pathogenetic mechanisms, and the therapeutic approach is continuously updated. Methods: We investigated how diagnosis and therapy were dealt with in the past and how researchers sought to understand, exactly, the pathogenetic biomolecular mechanisms of H. pylori, from the genesis of the infection to the current knowledge, with an analysis of carcinogenic mechanisms in the stomach. We have examined the scientific evolution of the knowledge of the disease over these 40 years in the gastroenterological and pharmacological fields. This was possible through a search in the databases of Medline, the WHO website, the Centers for Disease Control and Prevention (CDC) website, PubMed, and Web of Science to analyze the earlier and the latest data regarding H. pylori. Results: With the scientific discoveries over time, thanks to an increasing number of progressions in scientific research in the analysis of the gastric mucosa, the role of Helicobacter pylori in peptic ulcer, carcinogenesis, and in some forms of gastric lymphoma was revealed. Furthermore, over the years, the biomolecular mechanism involvement in some diseases has also been noted (such as cardiovascular ones), which could affect patients positive for H. pylori. Conclusions: Thanks to scientific and technological advances, the role of the bacterium H. pylori in carcinogenesis has been discovered and demonstrated, and new prospective research is currently attempting to investigate the role of other factors in the stomach and other organs. Cancer from H. pylori infection had a high incidence rate compared to various types of cancer, but in recent years, it is improving thanks to the techniques developed in the detection of the bacterium and the evolution of therapies. Thus, although it has become an increasingly treatable disease, there is still continuous ongoing research in the field of treatment for resistance and pharma compliance. Furthermore, in this field, probiotic therapy is considered a valid adjuvant.

Endoscopic Transnasal Odontoidectomy for Ventral Decompression of the Craniovertebral Junction: Surgical Technique and Clinical Outcome in a Case Series of 19 Patients.

Abnormalities and pathologies of the craniovertebral junction as well as space-occupying lesions of the odontoid process can result in myelopathy symptoms. A staged procedure with posterior stabilization and anterior transnasal endoscopic decompression is recently considered a less invasive alternative to the transoral approach. We present a considerably large case series focused on the operative technique and the long-term neurological clinical outcome. To determine the safety and efficacy of odontoidectomy performed via an endoscopic transnasal approach. We retrospectively reviewed all patients treated in our neurosurgical department from January 2009 to January 2020. Demographics, pre- and postoperative clinical status, and operative technique and complications were extracted and analyzed. In total, 22 transnasal operations were performed in 19 patients from January 2009 to January 2020. All but one patient underwent posterior C1-C2 instrumentation prior to the anterior transnasal computed tomography (CT)-navigated full-endoscopic decompression. The median duration of symptoms before surgery was 3 mo. Complications occurred in 1 patient who died from septic organ failure because of his initial diagnosis of osteomyelitis. Postoperative CT imaging showed sufficient decompression in 16 patients, and 3 patients underwent a transnasal endoscopic re-decompression (16%). Transnasal endoscopic odontoidectomy presents a safe procedure with a satisfying clinical and radiological postoperative outcome.

DETERMINING THE KNOWLEDGE, ATTITUDE AND THE BEHAVIOR OF PEOPLE LIVING IN DIFFERENT REGIONS OF TURKEY IN TERMS OF DENTAL PROCEDURES DURING COVID-19 PANDEMIC

In the end of December 2019, a virus disease that occurred in Wuhan City, China. The disease which is transmitted by droplets and contact is accepted as pandemic by the World Health Organization (WHO) was named as COVID-19. Clinical symptoms of COVID-19 are dry cough, shortness of breath and fever, but if the disease progress, some fatal complications can occur as septic shock, organ and system failure, pneumonia or Acute Respiratory Distress Syndrome (ARDS). This study was examined the knowledge, attitude, and behavior of People Living in Different Regions of Turkey in terms of dentistry procedures during new coronavirus outbreak. There were 438 respondents in the study. When the participants were asked what to do if they had toothache during the COVID-19 pandemic, only 56 people (12.8%) stated that they would go to the dentist, in addition, only 17.4% of the participants know that "severe toothache, dental abscess, jaw, and facial fractures and tooth dislocation as a result of trauma" are within the scope of emergency dental treatments. Our data revealed that health committees should do public health studies and use the media more in this regard in order to raise awareness of the people and eliminate information pollution.

The HDL from septic-ARDS patients with composition changes exacerbates pulmonary endothelial dysfunction and acute lung injury induced by cecal ligation and puncture (CLP) in mice

BackgroundSeptic-acute respiratory distress syndrome (ARDS), characterized by the acute lung injury (ALI) secondary to aberrant systemic inflammatory response, has high morbidity and mortality. Despite increased understanding of ALI pathogenesis, the therapies to prevent lung dysfunction underlying systemic inflammatory disorder remain elusive. The high density lipoprotein (HDL) has critical protective effects in sepsis and its dysfunction has a manifested contribution to septic organ failure. However, the adverse changes in HDL composition and function in septic-ARDS patients are large unknown.MethodsTo investigate HDL remodeling in septic-ARDS, we analyzed the changes of HDL composition from 40 patients with septic-ARDS (A-HDL) and 40 matched normal controls (N-HDL). To determine the deleterious functional remodeling of HDL, A-HDL or N-HDL was administrated to C57BL/6 and apoA-I knock-out (KO) mice after cecal ligation and puncture (CLP) procedure. Mouse lung microvascular endothelial cells (MLECs) were further treated by these HDLs to investigate whether the adverse effects of A-HDL were associated with endothelial dysfunction.ResultsSeptic-ARDS patients showed significant changes of HDL composition, accompanied with significantly decreased HDL-C. We further indicated that A-HDL treatment aggravated CLP induced ALI. Intriguingly, these deleterious effects of A-HDL were associated with pulmonary endothelial dysfunction, rather than the increased plasma lipopolysaccharide (LPS). Further in vitro results demonstrated the direct effects of A-HDL on MLECs, including increased endothelial permeability, enhanced expressions of adhesion proteins and pro-inflammatory cytokines via activating NF-κB signaling and decreased junction protein expression.ConclusionsOur results depicted the remodeling of HDL composition in sepsis, which predisposes lung to ARDS via inducing ECs dysfunction. These results also demonstrated the importance of circulating HDL in regulating alveolar homeostasis.

Sphingosine 1-phosphate escapes the Catch-22 of sepsis prevention and mitigation therapies.

Sepsis is defined as life-threatening organ dysfunction as a consequence of a dysregulated host immune response to infection and is the leading cause of mortality across the globe [1]. Septic organ dysfunction leads to a 2-2•5 times greater risk of death, and patients that progress to septic shock have hospital mortality rates greater than 40%. With few options available for prevention or treatment, antibiotics and supportive therapies are initiated empirically.

Circulating Methemoblogin Fraction in Dogs With Sepsis.

Large amount of nitric oxide (NO) can be released in patients with sepsis. Methemoglobin is formed from the interaction between NO and hemoglobin. Mild methemoglobinemia reflecting NO overproduction has been reported in septic people, and occasionally associated to septic shock and organ dysfunction. The aim of this retrospective study was to evaluate circulating methemoglobin fraction in dogs with sepsis and to assess its prognostic value. Methemoglobin reference interval (RI) was calculated in 41 healthy dogs and was set at 0–2.2%. A total of 131 dogs with sepsis were included in the study; 24/131 had a circulating methemoglobin ≥2.2%. The median methemoglobin fraction was significantly higher in dogs with sepsis compared to healthy ones (1.7%, 0.4–3.5% vs. 1.0, 0.3–2.2%, P = 0.0005). No significant difference was observed between dogs with uncomplicated sepsis (n = 98) vs. dogs with septic shock (n = 33) (1.8%, 0.4–2.8% vs. 1.5%, 0.4–3.5%, P = 0.74), between dogs with and without multi-organ dysfunction (n = 38 and n = 93, respectively) (1.7%, 0.4–3.5% vs. 1.7%, 0.5–2.8%, P = 0.27), and between survivors (n = 77) vs. non survivors (n = 54) (1.5%, 0.4–2.8% vs. 1.8%, 0.4–3.5%, P = 0.05). Dogs with methemoglobin fraction above or equal to the upper limit of the RI had a significantly higher frequency of death compared to dogs with methemoglobin levels <2.2% (60.0% vs. 36.8%, P = 0.04). In conclusion, mild methemoglobinemia is detected in dogs with sepsis, and methemoglobin values above the RI might be associated with a worse outcome.

The Warburg Effect Promotes Mitochondrial Injury Regulated by Uncoupling Protein-2 in Septic Acute Kidney Injury.

Evidence implying that metabolism reprogramming plays an important role in the regulation of sepsis is increasing; however, whether it has a similar role in septic organ dysfunction remains unclear. Here, we provide evidence to support a new role of uncoupling protein-2 (UCP2)-regulated Warburg effect, i.e., aerobic glycolysis, in promoting mitochondrial injury in the kidney. To imitate sepsis condition, male C57BL/6 mice were operated by the cecal ligation puncture in vivo, whereas a normal human kidney cell line (HK-2) was treated with lipopolysaccharide in vitro. UCP2 small interfering RNA pretreatment was performed to knock down UCP2 expression in vitro. The glycolysis metabolite was detected by liquid chromatography/tandem mass spectrometry in vivo and detected by commercial kits in vitro. Oxidative phosphorylation level and glycolysis level were monitored by measuring the oxygen consumption rate (indicative of respiration) and extracellular acidification rate (indicative of glycolysis) in vitro. Exogenous lactate was supplied to stimulate HK-2 cells and indicators of mitochondrial dysfunction were also assessed. Aerobic glycolysis is enhanced in septic tubular epithelial cells, and the glycolysis inhibitor 2-deoxyglucose can partially restore mitochondrial membrane potential and decrease the reactive oxygen species production. With the knockdown of UCP2, the aerobic glycolysis level upregulates, and mitochondrial injury increases. These results provide insights on a new mechanism of metabolic regulation of mitochondrial injury and the importance of targeting aerobic glycolysis for the treatment of septic acute kidney injury.

CD74 knockout protects against LPS-induced myocardial contractile dysfunction through AMPK-Skp2-SUV39H1-mediated demethylation of BCLB.

Lipopolysaccharides (LPS), an outer membrane component of Gram-negative bacteria, triggers myocardial anomalies in sepsis. Recent findings indicated a role for inflammatory cytokine MIF and its receptor, CD74, in septic organ injury, although little is known of the role of MIF-CD74 in septic cardiomyopathy. This study evaluated the impact of CD74 ablation on endotoxaemia-induced cardiac anomalies. Echocardiographic, cardiomyocyte contractile and intracellular Ca2+ properties were examined. Our data revealed compromised cardiac function (lower fractional shortening, enlarged LV end systolic diameter, decreased peak shortening, maximal velocity of shortening/relengthening, prolonged duration of relengthening and intracellular Ca2+ mishandling) and ultrastructural derangement associated with inflammation, O2 - production, apoptosis, excess autophagy, phosphorylation of AMPK and JNK and dampened mTOR phosphorylation. These effects were attenuated or mitigated by CD74 knockout. LPS challenge also down-regulated Skp2, an F-box component of Skp1/Cullin/F-box protein-type ubiquitin ligase, while up-regulating that of SUV39H1 and H3K9 methylation of the Bcl2 protein BCLB. These effects were reversed by CD74 ablation. In vitro study revealed that LPS facilitated GFP-LC3B formation and cardiomyocyte defects. These effects were prevented by CD74 ablation. Interestingly, the AMPK activator AICAR, the autophagy inducer rapamycin and the demethylation inhibitor difenoconazole inhibited the effects of CD74 ablation against LPS-induced cardiac dysfunction, while the SUV39H1 inhibitor chaetocin or methylation inhibitor 5-AzaC ameliorated LPS-induced GFP-LC3B formation and cardiomyocyte contractile dysfunction. Our data suggested that CD74 ablation protected against LPS-induced cardiac anomalies, O2 - production, inflammation and apoptosis through suppression of autophagy in a Skp2-SUV39H1-mediated mechanism.

Gene Expression of Protein Tyrosine Phosphatase 1B and Endoplasmic Reticulum Stress During Septic Shock.

Introduction: Protein Tyrosine Phosphatase 1B (PTP1B) and endoplasmic reticulum stress (ERS) are involved in the septic inflammatory response. Their inhibition is associated with improved survival in murine models of sepsis. The objective was to describe PTP1B and ERS expression during septic shock in human.Material and Methods: Prospective study including patients admitted to intensive care unit (ICU) for septic shock. Blood samples were collected on days 1 (D1), 3 and 5 (D5). Quantitative PCR (performed from whole blood) evaluated the expression of genes coding for PTP1B (PTPN1) and key elements of ERS (GRP78, ATF6, CHOP) or for endothelial dysfunction-related markers (ICAM1 and ET1). We analyzed gene variation between D5 and D1, collected glycemic parameters, insulin resistance and organ failure was evaluated by Sequential Organ Failure Assessment (SOFA) score.Results: We included 44 patients with a mean SAPS II 50 ± 16 and a mortality rate of 13.6%. Between D1 and D5, there was a significant decrease of PTPN1 (p < 0.001) and ATF6 (p < 0.001) expressions. Their variations of expression were correlated with SOFA variation (PTPN1, r = 0.35, CI 95% [0.05; 0.54], p = 0.03 and ATF6, r = 0.45 CI 95% [0.20; 0.65], p < 0.001). We did not find any correlation between PTPN1 expression and insulin resistance or glycemic parameters. Between D1 and D5, ATF6 and PTPN1 expressions were correlated with that of ET1.Conclusions: Our study has evaluated for the first time the expression of PTP1B and ERS in patients with septic shock, revealing that gene expression variation of PTPN1 and ATF6 are partly correlated with the evolution of septic organ failure and with endothelial dysfunction markers expression.

Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection

BackgroundMortality is high among patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. We aimed to determine hospital mortality and the factors associated with it in a cohort of MERS-CoV patients.MethodsWe reviewed hospital records of confirmed cases (detection of virus by polymerase chain reaction from respiratory tract samples) of MERS-CoV patients (n = 63) admitted to Buraidah Central Hospital in Al-Qassim, Saudi Arabia between 2014 and 2017. We abstracted data on demography, vital signs, associated conditions presented on admission, pre-existing chronic diseases, treatment, and vital status. Bi-variate comparisons and multiple logistic regressions were the choice of data analyses.ResultsThe mean age was 60 years (SD = 18.2); most patients were male (74.6%) and Saudi citizens (81%). All but two patients were treated with Ribavirin plus Interferon. Hospital mortality was 25.4%. Patients who were admitted with septic shock and/or organ failure were significantly more likely to die than patients who were admitted with pneumonia and/or acute respiratory distress syndrome (OR = 47.9, 95% CI = 3.9, 585.5, p-value 0.002). Age, sex, and presence of chronic conditions were not significantly associated with mortality.ConclusionHospital mortality was 25%; septic shock/organ failure at admittance was a significant predictor of mortality.

A multiplex analysis of sepsis mediators during human septic shock: a preliminary study on myocardial depression and organ failures

BackgroundThe mechanisms of organ failure during sepsis are not fully understood. The hypothesis of circulating factors has been suggested to explain septic myocardial dysfunction. We explored the biological coherence of a large panel of sepsis mediators and their clinical relevance in septic myocardial dysfunction and organ failures during human septic shock.MethodsPlasma concentrations of 24 mediators were assessed on the first day of septic shock using a multi-analyte cytokine kit. Septic myocardial dysfunction and organ failures were assessed using left ventricle ejection fraction (LVEF) and the Sequential Organ Failure Assessment score, respectively.ResultsSeventy-four patients with septic shock (and without immunosuppression or chronic heart failure) were prospectively included. Twenty-four patients (32%) had septic myocardial dysfunction (as defined by LVEF < 45%) and 30 (41%) died in ICU. Hierarchical clustering identified three main clusters of sepsis mediators, which were clinically meaningful. One cluster involved inflammatory cytokines of innate immunity, most of which were associated with septic myocardial dysfunction, organ failures and death; inflammatory cytokines associated with septic myocardial dysfunction had an additive effect. Another cluster involving adaptive immunity and repair (with IL-17/IFN pathway and VEGF) correlated tightly with a surrogate of early sepsis resolution (lactate clearance) and ICU survival.ConclusionsIn this preliminary study, we identified a cluster of cytokines involved in innate inflammatory response associated with septic myocardial dysfunction and organ failures, whereas the IL-17/IFN pathway was associated with a faster sepsis resolution and a better survival.

Hospital-acquired pneumonia - new guidelines

The role of multidrug-resistant (MDR) pathogens in nosocomial infections is increasing. However national data in Germany do not show significant changes in the spectrum of pathogens in hospital-acquired pneumonia (HAP). The assessment of individual risk factors for MDR pathogens remains central for the selection of empiric antimicrobial therapy. Thoracic ultrasound may be added as part of the diagnostic work-up and for the detection of complications. Procalcitonin and lactate testing are recommended for the diagnosis of sepsis/septic shock in addition to sepsis scores. Detection of influenza virus by PCR from respiratory samples is recommended during influenza season. Empiric combination therapy is only recommended for patients with severe HAP (invasive ventilation, septic shock) and high risk of infection with MDR pathogens, since combination therapy has only been shown to be superior in this situation. Deescalation according to clinical and microbiological criteria is highly recommended. In patients with septic organ dysfunction/septic shock antibiotic dosing of adequately choosen betalactams according to Pk/Pd criteria is endorsed. adjunctive aerosolised therapy should only be performed in experienced centres. This remains an option for patients with detection of MDR pathogens, who are not deemed successfully treatable with systemic therapy alone.

Circulating cell death biomarker TRAIL is associated with increased organ dysfunction in sepsis.

In sepsis, there may be dysregulation in programed cell death pathways, typified by apoptosis and necroptosis. Programmed cell death pathways may contribute to variability in the immune response. TRAIL is a potent inducer of apoptosis. Receptor-interacting serine/threonine protein kinase-3 (RIPK3) is integral to the execution of necroptosis. We explored whether plasma TRAIL levels were associated with in-hospital mortality, organ dysfunction, and septic shock. We also explored the relationship between TRAIL and RIPK3. We performed an observational study of critically ill adults admitted to intensive care units at 3 academic medical centers across 2 continents, using 1 as derivation and the other 2 as validation cohorts. Levels of TRAIL were measured in the plasma of 570 subjects by ELISA. In all cohorts, lower (<28.5 pg/ml) versus higher levels of TRAIL were associated with increased organ dysfunction (P ≤ 0.002) and septic shock (P ≤ 0.004). Lower TRAIL levels were associated with in-hospital mortality in 2 of 3 cohorts (Weill Cornell-Biobank of Critical Illness, P = 0.012; Brigham and Women's Hospital Registry of Critical Illness, P = 0.011; Asan Medical Center, P = 0.369). Lower TRAIL was also associated with increased RIPK3 (P ≤ 0.001). Lower levels of TRAIL were associated with septic shock and organ dysfunction in 3 independent ICU cohorts. TRAIL was inversely associated with RIPK3 in all cohorts. NIH (R01-HL055330 and KL2-TR002385).

Early Sepsis Detection with Deep Learning on EHR Event Sequences

Background: Sepsis is a clinical condition involving an extreme inflammatory response to an infection, and is associated with high morbidity and mortality. Without intervention, this response can progress to septic shock, organ failure and death. Every hour that treatment is delayed mortality increases. Early identification of sepsis is therefore important for a positive outcome.&#x0D; Methods: We constructed predictive models for sepsis detection and performed a register-based cohort study on patients from four Danish municipalities. We used event-sequences of raw electronic health record (EHR) data from 2013 to 2017, where each event consists of three elements: a timestamp, an event category (e.g. medication code), and a value. In total, we consider 25.622 positive (SIRS criteria) sequences and 25.622 negative sequences with a total of 112 million events distributed across 64 different hospital units. The number of potential predictor variables in raw EHR data easily exceeds 10.000 and can be challenging for predictive modeling due to this large volume of sparse, heterogeneous events. Traditional approaches have dealt with this complexity by curating a limited number of variables of importance; a labor-intensive process that may discard a vast majority of information. In contrast, we consider a deep learning system constructed as a combination of a convolutional neural network (CNN) and long short-term memory (LSTM) network. Importantly, our system learns representations of the key factors and interactions from the raw event sequence data itself.&#x0D; Results: Our model predicts sepsis with an AUROC score of 0.8678, at 11 hours before actual treatment was started, outperforming all currently deployed approaches. At other prediction times, the model yields following AUROC scores. 15 min: 0.9058, 3 hours: 0.8803, 24 hours: 0.8073.&#x0D; Conclusion: We have presented a novel approach for early detection of sepsis that has more true positives and fewer false negatives than existing alarm systems without introducing domain knowledge into the model. Importantly, the model does not require changes in the daily workflow of healthcare professionals at hospitals, as the model is based on data that is routinely captured in the EHR. This also enables real-time prediction, as healthcare professionals enters the raw events in the EHR.

Corticosteroids for Septic Shock: Another Chapter in the Saga.

The use of corticosteroids in the management of septic shock has been a highly debated topic for quite some time. Corticosteroids have the ability to combat hyperinflammatory and exaggerated vasodilatory responses, as well as to sensitize adrenergic receptors to decrease the duration of shock. While helpful clinically, this has not translated to consistent mortality benefits. Conflicting results from 2 landmark trials published in 2002 and 2008 have led to varying clinical practices, and a clearly defined role of corticosteroids in septic shock is lacking. A decade later, an influx of new data derived from 2 more large trials continues to echo diverging viewpoints regarding patient mortality. In combination with fluctuating study designs (eg, adjunctive therapies and shock management) and patient populations (eg, illness severity), generalized conclusions are still difficult to draw. Despite these challenges, this review critically analyzes recently published data in the context of historical debate to provide an updated comment on the role of corticosteroids in septic shock. In summary, hydrocortisone therapy is likely to demonstrate maximal benefit when initiated on patients with septic shock and organ failure refractory to vasopressor therapy and should be used judiciously in other settings as it comes without a demonstrated benefit in mortality and increased potential for adverse effects.

The Role of ALDH2 in Sepsis and the To-Be-Discovered Mechanisms.

Sepsis, defined as life-threatening tissue damage and organ dysfunction caused by a dysregulated host response to infection, is a critical disease which imposes global health burden. Sepsis-induced organ dysfunction, including circulatory and cardiac dysfunction, hepatic dysfunction, renal dysfunction, etc., contributes to high mortality and long-term disability of sepsis patients. Altered inflammatory response, ROS and reactive aldehyde stress, mitochondrial dysfunction, and programmed cell death pathways (necrosis, apoptosis, and autophagy) have been demonstrated to play crucial roles in septic organ dysfunction. Unfortunately, except for infection control and supportive therapies, no specific therapy exists for sepsis. New specific therapeutic targets are highly warranted. Emerging studies suggested a role of potential therapeutic target of ALDH2, a tetrameric enzyme located in mitochondria to detoxify aldehydes, in septic organ dysfunction. In this article, we will review the presentations and pathophysiology of septic organ dysfunction, as well as summarize and discuss the recent insights regarding ALDH2 in sepsis.

敗血症性多臓器障害治療中に気管軟化症が明らかになり気管ステント留置を行った1例(A case of tracheal stenting in a tracheomalacia patient associated with septic organ failure)

要旨気管軟化症は気管壁の脆弱性に伴う気管の呼気性狭窄であり，保存的治療に抵抗性であることが多い。今回，遷延する敗血症性多臓器障害の治療中に発覚した気管軟化症に対し，気管ステントを留置した症例を経験したので報告する。症例は，気管支喘息の既往がある76歳の女性。呼吸苦と意識障害を主訴に救急搬送された。肺炎およびCO2ナルコーシスを認め，ICUで人工呼吸管理を開始したが，薬剤治療抵抗性の呼気性喘鳴を伴う換気不良が続いた。第36病日に気管支鏡にて気管軟化症と診断し，意識障害や凝固異常を合併していたが，人工呼吸器依存状態が遷延していたため，全身麻酔下にY字シリコンステント挿入を決断した。ステント留置後は気道狭窄音が消失したが，敗血症性多臓器不全のため第78病日に死亡した。気管軟化症は気管支喘息と誤診されやすく，来院時CTでも気管横径は短縮していたため，本症例は来院前より気管軟化症を呈していた可能性が高い。気管ステントは手術に比して低侵襲であるため，敗血症性多臓器障害を来した患者にも留置できた。本症例は，喘息の既往歴やCTによる気管径短縮の所見から早期に気管軟化症を疑うべきであった。呼気時気道狭窄の原因として常に気管軟化症を鑑別にあげ，早期診断することが重要である。

Prognostic score in patients with pyogenic liver abscess-our results in surgical outcome and lethality predicting

Introduction: Pyogenic liver abscess (PLA) is a disease with formation of inflammatory isle in the liver parenchima with cavity with purulent collection. Aim The purpose of this study is to analyze the lethal cases in patients with PLA and create a prognostic index , which could provide the final outcome of treatment. Materials and methods: In our study we included 89 cases of PLA. We performed retro - prospective study in the period 2004-2009- we had 51 patients, and a prospective part - the period 2010-2017 with proven 38 patients. Results: We have 6 fatal cases - overall mortality rate of 7.6 %. Based on the SOFA Score (Septic Organ Failure Assessment score) we try to predict lethality in patients with PLA. After analyzing the lethal cases, we found that in 5 of 6 cases have a high SOFA score total> 10 points. Regarding the aim to create a prognostic index to assess the severity of the disease and treatment outcome "we used cross- tabulations and chi-square to match SOFA index and any of the following values: I value “ Immune deficiency”, II-Risk pathogenesis of abscess, III- Positive blood culture. Conclusion: The evaluation of the "critical point ” showed that the index > 9.5 sensitivity 80% and specificity was 87% ( 1-0129 = 87.1% ) Keywords pyogenic liver abscess, lethality, SOFA score.

Streptococcal M1 protein induces hyporesponsiveness and cytokine release from human arteries in a fibrinogen-dependent manner: a translational study

BackgroundStreptococcus pyogenes is a Gram positive bacterial species commonly involved in sepsis. Invasive strains express virulence factors such as the M1 protein. M1 protein forms complexes with fibrinogen leading to a cytokine storm in plasma contributing to the development of septic shock and organ failure. In experimental animals M1 protein causes vascular nitric oxide production and hyporesponsiveness to pressors, but it is not known whether it affects the human vascular wall.MethodsHuman omental arteries obtained during surgery were incubated in vitro with M1 protein or lipopolysaccharide (LPS) as positive control, with or without plasma. After 48 h, contractile response to noradrenaline was measured, and levels of nitrite/nitrate and the cytokines interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in the incubation medium were measured. A second set of arteries were incubated with or without main components of plasma (immunoglobulin G, albumin or fibrinogen), in the presence of M1 protein followed by cytokine measurement.ResultsArtery segments incubated with M1 protein and plasma contracted weaker in response to noradrenaline, and levels of IL-6 and IL-8 were significantly higher compared to after incubation with M1 protein alone. Incubation with M1 protein and fibrinogen resulted in elevated levels of IL-6 and IL-8, while incubation with M1 protein and albumin or immunoglobulin G did not affect the levels. Neither any of the other cytokines nor nitrite/nitrate was detected in the medium in any of the incubation conditions.ConclusionsThe study shows that M1 protein of Streptococcus pyogenes has a direct effect on the human vascular wall in the presence of plasma, demonstrated both as a diminished contractile response to noradrenaline and increased cytokine production. The effect of plasma was attributed to fibrinogen. The findings suggest that M1 protein contributes to the development of septic shock through impairment of the contractility of the vascular wall.

Fms-Like Tyrosine Kinase-3 Ligand Attenuates Local and Systemic Infection in a Model of Post-Burn Pneumonia.

Burn injury induces immunosuppression and promotes infection with opportunistic pathogens. Pneumonia and sepsis are leading causes of post-burn morbidity and mortality. Fms-like tyrosine kinase-3 ligand (Flt3L) improves local and systemic resistance to P aeruginosa-associated burn wound infection. This study evaluates the effects of post-burn prophylactic Flt3L treatment on local and systemic infection and inflammation in a murine model of pneumonia and sepsis. Mice received a severe scald burn, were treated with Flt3L or vehicle (CTR) for 5 days, and inoculated trans-nasally with P aeruginosa. Lung, blood, and spleen were harvested at 24 and 48 h postinoculation (p.i.) to assess infection (bacterial burden, bacteremia, distant organ manifestation) and inflammation (interleukin-6 (IL-6) and myeloperoxidase (MPO) levels). Histology correlated infection and inflammation parameters with morphology. Survival at various bacterial concentrations was monitored for 14 days p.i. Bacterial burden was significantly reduced in lung and spleen of Flt3L-treated mice. Flt3L treatment was associated with decreased signs of pulmonary inflammation (reduced wet weight and IL-6 levels), lower incidences of bacteremia and septic distant organ manifestation, and reduced systemic inflammation (IL-6 and MPO). Histologically, reduced alveolar and peribronchiolar neutrophil and lymphocyte infiltration indicated attenuated pulmonary inflammation after Flt3L treatment. Overall survival was comparable between groups for all doses of P aeruginosa, but mortality delayed in the Flt3L-treated group. Prophylactic treatment with Flt3L could augment antimicrobial therapy of post-burn pneumonia through improvement of the initial host response to challenge with P aeruginosa, attenuate local, and systemic inflammation as well as septic pathogen dissemination.