論文紹介 好中球機能

急性期免疫管理ブランチ2015

本年は，集中治療管理に免疫管理の重要性を盛り込んだものですから，

国内のいろいろな講演でも，一部を紹介していきます。

以下の論文は，本年の私のMEIDAI免疫管理バンドルの「好中球ブランチ」の中で紹介する文献です。

Crit Care. 2015 Feb 25;19(1):57. doi: 10.1186/s13054-015-0778-z.

The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation.

Mare TA1,2, Treacher DF3,4, Shankar-Hari M5,6, Beale R7,8, Lewis SM9,10,11, Chambers DJ12, Brown KA13,14,15.

Author information

 

Abstract

INTRODUCTION: 

In this cohort study, we investigated whether monitoring blood levels of immature neutrophils (myelocytes, metamyelocytes and band cells) differentiated patients with sepsis from those with the non-infectious (N-I) systemic inflammatory response syndrome (SIRS). We also ascertained if the appearance of circulating immature neutrophils was related to adverse outcome.

METHODS: 

Blood samples were routinely taken from 136 critically ill patients within 48 hours of ICU entry and from 20 healthy control subjects. Clinical and laboratory staff were blinded to each other's results, and patients were retrospectively characterised into those with SIRS (n = 122) and those without SIRS (n = 14). The patients with SIRS were further subdivided into categories of definite sepsis (n = 51), possible sepsis (n = 32) and N-I SIRS (n = 39). Two established criteria were used for monitoring immature white blood cells (WBCs): one where band cells >10% WBCs and the other where >10% of all forms of immature neutrophils were included but with a normal WBC count. Immature neutrophils in blood smears were identified according to nuclear morphology and cytoplasmic staining.

RESULTS: 

With the first criterion, band cells were present in most patients with SIRS (mean = 66%) when compared with no SIRS (mean = 29%; P

CONCLUSIONS: 

Raised blood levels of band cells have diagnostic significance for sepsis, provided that measurements are not confined to patients with normal WBC counts, whereas an increased prevalence of myelocytes and metamyelocytes may have prognostic application.

 

Crit Care Med. 2013 Mar;41(3):820-32. doi: 10.1097/CCM.0b013e318274647d.

Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome.

Drifte G1, Dunn-Siegrist I, Tissières P, Pugin J.

Author information

 

Abstract

OBJECTIVE: 

A hallmark of sepsis and severe systemic inflammatory response syndrome (SIRS) is the massive recruitment of immature neutrophils from the bone marrow into the circulation (left shift, band forms). Their capacity to participate in innate defense against bacteria is ill defined. We aimed at comparing various innate immune functions of mature vs. immature neutrophils circulating during sepsis and SIRS.

DESIGN: 

Prospective, observational cohort study.

SETTING:Tertiary level ICU and associated research laboratory.

PATIENTS: 

Thirty-three ICU patients with sepsis; 12 ICUs with SIRS; 32 healthy volunteers.

INTERVENTIONS: 

Twenty milliliters of whole heparinized blood was used for in vitro studies including neutrophil viability and apoptosis, surface expression of CD16, Toll-like receptors () 4 and TLR2, CD14, MD-2, HLA-DP,-DQ and -DR, and CXCR2, chemotaxis, phagocytosis, bacterial killing, and tumor necrosis factor-α/interleukin-10 baseline intracellular cytokine levels.

MEASUREMENTS AND MAIN RESULTS: 

Immature neutrophils were capable of mediating important innate immune functions such as bacterial phagocytosis and killing via the production of reactive oxygen species, although less efficiently than mature neutrophils. Immature neutrophils had a longer life span and resistance to spontaneous apoptosis, and could mature ex vivo. They expressed lower levels of receptors for bacterial molecules such as CD14 and MD-2 and migrated less efficiently than mature granulocytes. Immature neutrophils had higher basal intracellular tumor necrosis factor-α/interleukin-10 ratio than that of mature neutrophils, suggesting a proinflammatory phenotype. No significant differences were observed between immature neutrophils isolated from patients with sepsis and those from patients with severe SIRS.

CONCLUSIONS: 

Despite their "immaturity", band forms are capable of mediating crucial innate immune functions during severe infections and sepsis. Their fate and capacity to mature in vivo remain to be determined.

総説 Clostridium Difficile 感染症

Clostridium difficile infection.
Leffler DA, Lamont JT.
N Engl J Med. 2015 Apr 16;372(16):1539-48. doi: 10.1056/NEJMra1403772.


Clostridium difficile is an anaerobic gram-positive, spore-forming, toxin-producing bacillus that is transmitted among humans through the fecal–oral route. The relationship between the bacillus and humans was once thought to be commensal,1 but C. difficile has emerged as a major enteric pathogen with worldwide distribution. In the United States, C. difficile is the most frequently reported nosocomial pathogen. A surveillance study in 2011 identified 453,000 cases of C. difficile infection and 29,000 deaths associated with C. difficile infection; approximately a quarter of those infections were community-acquired.2 Nosocomial C. difficile infection more than quadruples the cost of hospitalizations,3 increasing annual expenditures by approximately $1.5 billion in the United States.4 In this article, we review the changing epidemiology of this infection, discuss risk factors and preventive strategies, outline current recommendations for treatment, and highlight developing strategies for disease control.







Figure 3. Rates of Cure and Changes to the Microbiota after Fecal Microbial Transplantation for Recurrent Clostridium difficile Infection.
Among patients with recurrent C. difficile infection, the rate of cure without relapse was higher among those who received an infusion of donor feces than among those who received vancomycin with or without bowel lavage (Panel A). Fecal microbial diversity in recipients before and after the infusion of donor feces is compared with the diversity in healthy donors (Panel B). Microbial diversity is expressed by Simpson’s Reciprocal Index. The index ranges from 1 to 250, with higher values indicating more diversity. The box- and-whisker plots indicate interquartile ranges (boxes), medians (dark hori- zontal lines in the boxes), and highest and lowest values (whiskers above and below the boxes).
van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal infusion of donor feces for recurrent Clostridium difficile. N Engl J Med 2013;368:407-15.

臨床研究 重症敗血症罹患後の1年後を考える

Increased 1-Year Healthcare Use in Survivors of Severe Sepsis
Hallie C. Prescott1, Kenneth M. Langa1,2,3, Vincent Liu4, Gabriel J. Escobar4, and Theodore J. Iwashyna1,2,3

1Department of Medicine, University of Michigan, Ann Arbor, Michigan
2VA Center for Clinical Management Research, HSR&D Center for Excellence, Ann Arbor, Michigan
3Institute for Social Research, Ann Arbor, Michigan; and
4Kaiser Permanente Division of Research, Oakland, California
Corresponding Author: Hallie C. Prescott


Rationale:
Hospitalizations for severe sepsis are common, and a growing number of patients survive to hospital discharge. Nonetheless, little is known about survivors’ post-discharge healthcare use.

Objectives:
To measure inpatient healthcare use of severe sepsis survivors compared with patients’ own presepsis resource use and the resource use of survivors of otherwise similar nonsepsis hospitalizations.

Methods:
This is an observational cohort study of survivors of severe sepsis and nonsepsis hospitalizations identified from participants in the Health and Retirement Study with linked Medicare claims, 1998–2005. We matched severe sepsis and nonsepsis hospitalizations by demographics, comorbidity burden, premorbid disability, hospitalization length, and intensive care use.

Measurements and Main Results:
Using Medicare claims, we measured patients’ use of inpatient facilities (hospitals, long-term acute care hospitals, and skilled nursing facilities) in the 2 years surrounding hospitalization. Severe sepsis survivors spent more days (median, 16 [interquartile range, 3–45] vs. 7 [0–29]; P < 0.001) and a higher proportion of days alive (median, 9.6% [interquartile range, 1.4&#8211;33.8%] vs. 1.9% [0.0&#8211;7.9%]; P < 0.001) admitted to facilities in the year after hospitalization, compared with the year prior. The increase in facility-days was similar for nonsepsis hospitalizations. However, the severe sepsis cohort experienced greater post-discharge mortality (44.2% [95% confidence interval, 41.3&#8211;47.2%] vs. 31.4% [95% confidence interval, 28.6&#8211;34.2%] at 1 year), a steeper decline in days spent at home (difference-in-differences, －38.6 d [95% confidence interval, －50.9 to 26.3]; P < 0.001), and a greater increase in the proportion of days alive spent in a facility (difference-in-differences, 5.4% [95% confidence interval, 2.8&#8211;8.1%]; P < 0.001).

<font size="4">Conclusions:
Healthcare use is markedly elevated after severe sepsis, and post-discharge management may be an opportunity to reduce resource use.