A longitudinal change of syndecan-1 predicts risk of acute respiratory distress syndrome and cumulative fluid balance in patients with septic shock: a preliminary study.

BACKGROUND: The purpose of this study is to investigate the time course of syndecan-1 (Syn-1) plasma levels, the correlation between Syn-1 and organ damage development, and the associations of Syn-1 level with cumulative fluid balance and ventilator-free days (VFD) in patients with septic shock. METHODS: We collected blood samples from 38 patients with septic shock upon their admission to ICU and for the first 7 days of their stay. Syn-1 plasma level, acute respiratory distress syndrome (ARDS), other organ damage, VFD, and cumulative fluid balance were assessed daily. RESULTS: Over the course of 7 days, Syn-1 plasma levels increased significantly more in patients with ARDS than in those without ARDS. Patients with high levels of Syn-1 in the 72 h after ICU admission had significantly higher cumulative fluid balance, lower PaO2/FiO2, and fewer VFD than patients with low levels of Syn-1. Syn-1 levels did not correlate with sequential organ failure assessment score or with APACHE II score. CONCLUSIONS: In our cohort of patients with septic shock, higher circulating level of Syn-1 of cardinal glycocalyx component is associated with more ARDS, cumulative positive fluid balance, and fewer VFD. Measurement of Syn-1 levels in patients with septic shock might be useful for predicting patients at high risk of ARDS.

Usefulness of serum procalcitonin for necrotizing fasciitis as an early diagnostic tool.

INTRODUCTION: While the early diagnosis of necrotizing fasciitis (NF) is crucial and could lead to a favorable outcome, it is difficult to differentiate NF from cellulitis, resulting in delay for the appropriate treatment. PATIENTS AND METHODS: For the purpose of examining which diagnostic tools could correctly differentiate NF from cellulitis, we conducted this case-control study. We retrospectively reviewed all patients who were diagnosed with NF at our institute during 2014-2019. The patients who were diagnosed with cellulitis were randomly selected during the study period as the control group. The severity of NF is evaluated by serum-procalcitonin (PCT), LRINEC score, NTSI assessment and SIARI score. RESULTS: A total of 25 NF patients were enrolled in this study. The median age was 68 years (range 39-79) and 18 (72%) were male. Comparing NF and cellulitis groups, NF group showed a higher LRINEC score and serum PCT than cellulitis group did, even though there was no statistical significance in serum PCT. With respect to the diagnostic value for differentiating NF from cellulitis, the area under the ROC curve for of serum PCT and LRINEC scores were 0.928 [95% confidential interval (CI) 0.864-0.992, p < 0.001] and 0.846 (95% CI 0.757-0.936, p < 0.001). The appropriate serum-PCT cutoff value was 1.0 and had a sensitivity of 88%, a specificity of 89%, a positive predictive value of 81%, and a negative predictive value of 93%. CONCLUSION: Serum-PCT could be a useful diagnostic marker for differentiating diagnosis of NF from cellulitis.

Removal of Circulating Neutrophil Extracellular Trap Components With an Immobilized Polymyxin B Filter: A Preliminary Study.

Components of neutrophil extracellular traps (NETs) are released into the circulation by neutrophils and contribute to microcirculatory disturbance in sepsis. Removing NET components (DNA, histones, and proteases) from the circulation could be a new strategy for counteracting NET-dependent tissue damage. We evaluated the effect of hemoperfusion with a polymyxin B (PMX) cartridge, which was originally developed for treating gram-negative infection, on circulating NET components in patients with septic shock, as well as the effect on phorbol myristate acetate (PMA)-stimulated neutrophils obtained from healthy volunteers. Ex vivo closed loop hemoperfusion was performed through PMX filters in a laboratory circuit. Whole blood from healthy volunteers (incubated with or without PMA) or from septic shock patients was perfused through the circuit. For in vivo experiment blood samples were collected before and immediately after hemoperfusion with PMX to measure the plasma levels of cell-free NETs. The level of cell-free NETs was assessed by measuring myeloperoxidase-associated DNA (MPO-DNA), neutrophil elastase-associated DNA (NE-DNA), and cell-free DNA (cf-DNA). Plasma levels of MPO-DNA, NE-DNA, and cf-DNA were significantly increased after 2 h of PMA stimulation. When the circuit was perfused with blood from septic shock patients or PMA-stimulated neutrophils from healthy volunteers, circulating levels of MPO-DNA, NE-DNA, and cf-DNA were significantly reduced after 1 and 2 h of perfusion with a PMX filter compared with perfusion without a PMX filter. In 10 patients with sepsis, direct hemoperfusion through filters with immobilized PMX significantly reduced plasma levels of MPO-DNA and NE-DNA. These ex vivo and in vivo findings demonstrated that hemoperfusion with PMX removes circulating NET components. Selective removal of circulating NET components from the blood could be effective for prevention/treatment of NET-related inappropriate inflammation and thrombogenesis in patients with sepsis.

Increased PD-1 Expression and Altered T Cell Repertoire Diversity Predict Mortality in Patients with Septic Shock: A Preliminary Study.

Sepsis causes impairment of innate and adaptive immunity by multiple mechanisms, including depletion of immune effector cells and T cell exhaustion. Although lymphocyte dysfunction is associated with increased mortality and potential reactivation of latent viral infection in patients with septic shock, the relation between viral reactivation and lymphocyte dysfunction is obscure. The objectives of this study were 1) to determine the relation of lymphocyte dysfunction to viral reactivation and mortality, and 2) to evaluate recovery of lymphocyte function during septic shock, including T cell receptor (TCR) diversity and the expression of programmed death 1 (PD-1). In 18 patients with septic shock and latent cytomegalovirus (CMV) infection, serial blood samples were obtained on days 1, 3, and 7 after the onset of shock, and immune cell subsets and receptor expression were characterized by flow cytometry. TCR diversity of peripheral blood mononuclear cells was analyzed by Multi-N-plex PCR, and CMV DNA was quantified using a real-time PCR kit. A decrease of TCR diversity and monocyte HLA-DR expression were observed in the early stage of septic shock, while CD4+ T cells displayed an increase of PD-1 expression. Significant lymphopenia persisted for at least 7 days following the onset of septic shock. Normalization of TCR diversity and PD-1 expression was observed by day 7, except in patients who died. CMV reactivation was detected in 3 of the 18 patients during the first week of their ICU stay and all 3 patients died. These changes are consistent with the early stage of immune cell exhaustion and indicate the importance of normal lymphocyte function for recovery from septic shock. Ongoing lymphocyte dysfunction is associated with CMV reactivation and dissemination, as well as with unfavorable outcomes.

Clostridium Perfringens Infection in a Febrile Patient with Severe Hemolytic Anemia.

BACKGROUND: Clostridium perfringens (C. perfringens) can cause various infections, including gas gangrene, crepitant cellulitis, and fasciitis. While C. perfringens sepsis is uncommon, it is often rapidly fatal because the alpha toxin of this bacterium induces massive intravascular hemolysis by disrupting red blood cell membranes. CASE REPORT: We present the case of a male patient with diabetes who developed a fatal liver abscess with massive intravascular hemolysis and septic shock caused by toxigenic C. perfringens. The peripheral blood smear showed loss of central pallor, with numerous spherocytes. Multiplex PCR only detected expression of the cpa gene, indicating that the pathogen was C. perfringens type A. CONCLUSIONS: C. perfringens infection should be considered in a febrile patient who has severe hemolytic anemia with a very low MCV, hemolyzed blood sample, and negative Coombs test. The characteristic peripheral blood smear findings may facilitate rapid diagnosis.

Successful treatment of septic shock due to New Delhi metallo-ß-lactamase-1-producing Klebsiella pneumoniae in a patient transferred from India to Japan.

CASE: Here we report the fifth case of New Delhi metallo-ß-lactamase-1-producing Enterobacteriaceae infection in Japan. A 39-year-old Japanese man suffered a subarachnoid hemorrhage due to rupture of aneurysm in India. Once he was deemed stable enough, he was transferred from a hospital in India to our hospital in Japan. On day 5 after transfer, the patient suddenly developed septic shock and multidrug-resistant Klebsiella pneumoniae was isolated from a blood culture. OUTCOME: Treatment with colistin and high-dose meropenem as well as organ support were initiated, resulting in successful resolution of septic shock. This K. pneumoniae was shown to carry blaNDM-1 by polymerase chain reaction analysis. CONCLUSION: Our case suggests that New Delhi metallo-ß-lactamase-1-producing bacteria could be introduced into Japan easily. It is important to apply strict surveillance and infection control measures to prevent the spread of carbapenem resistance genes to Enterobacteriaceae in Japan.

Delayed myocardial injury following acute hydrogen sulfide intoxication.

INTRODUCTION: Hydrogen sulfide is a toxic, colorless gas produced by decaying organic matter. Its toxic effects are due to blocking of cellular respiratory enzymes, leading to anoxia. CASE PRESENTATION: We report a 28-year-old man who attempted suicide using hydrogen sulfide gas. When the emergency service arrived, his friend was dead and the patient was unconscious. He received supportive treatment and survived. In this patient both skeletal muscle and myocardial injury was observed after hydrogen sulfide intoxication. Skeletal muscle damage occurred first, because enzymes peak consisted of creatine phosphokinase, aspartate aminotransferase, and myoglobin was observed on hospital day 4. Myocardial injury was apparent on hospital day 15, because the subsequent enzymes peak was comprised of cardiac enzymes and associated electrocardiographic abnormalities. On hospital day 3, myocardial injury was detected and it evolved over the next 3 weeks to recover completely. CONCLUSION: The mechanisms of rhabdomyolysis and myocardial injury resulting from hydrogen sulfide poisoning are not known, but may be related to cellular anoxia or a direct toxic effect. This case highlights not only the risk of delayed cardiac damage, but also rhabdomyolysis, and emphasizes that careful monitoring of cardiac function and of the levels of skeletal muscle-related enzymes is essential for victims of hydrogen sulfide poisoning.

Time to initiation of treatment with polymyxin B cartridge hemoperfusion in septic shock patients.

BACKGROUND: We investigated whether early initiation of hemoperfusion with a polymyxin B cartridge (PMX) after the diagnosis of septic shock could improve the clinical outcome. METHODS: A prospective, open-labeled, multicenter cohort study was performed at intensive care units in Japan. 41 patients received PMX within 6 h after the diagnosis of septic shock (early group) and 51 patients were treated after 6 h (late group). RESULTS: The early group had a significantly shorter duration of ventilator support and also had a lower catecholamine requirement. PMX was effective for improvement of hypotension, hypoperfusion, the sequential organ failure assessment score, and pulmonary oxygenation regardless of the timing of its initiation. The 28-day mortality rate did not differ between the two groups. CONCLUSIONS: Early initiation of PMX shortened the duration of ventilator support and also reduced the catecholamine requirement, so early treatment of septic shock should achieve a better outcome.

Mediastinal myelolipoma.

Myelolipoma is a rare tumor, and a mediastinal location is extremely unusual. The main pathologic feature is the coexistence of mature adipose tissue and bone marrow cells; the presence of megakaryocytes is essential for diagnosis. The successful removal of a mediastinal myelolipoma in a 59-year-old man is described.