Acute respiratory distress syndrome is a type of non-cardiogenic respiratory failure characterized by rapid widespread inflammation in the lungs. Causes include pneumonia, sepsis, major trauma, severe burn, poisoning and autoimmune diseases. It is known that neutrophils have association with the pathophysiology of ARDS, while the mechanisms of ARDS progression has yet been fully elucidated. Neutrophil Extracellular Traps (NETs), which was first reported in 2004, are networks released from activated neutrophils, and they are composed of DNA from neutrophils, histone protein or various protease. They are thought to be a type of innate immunity and recently it has been revealed that the release of NETs may interact with activated platelets and vascular endothelium. The associations of NETs and ARDS have also been gradually elucidated. In future, the control of NETs release may become a target of ARDS therapy. We also reported two cases with serial changes of NETs formation in ARDS patients.

Over the last decades, it has become clear that platelets play an important role in the immune response in sepsis. Platelet derived microvesicles share certain characteristics with platelets, and also it acts as a mediator in cell to cell communication. It has been brought into the spotlight the platelet derived microvesicles deliver microRNA to the other cells and induce RNA Interference. Further studies are warranted to investigate the specific roles of the microRNAs in the pathogenesis of sepsis and the mechanism of delivery system.

Bone marrow-derived stem cells therapy had anti-inflammatory and regenerative properties, and was reported to reduce the acute inflammatory response caused by myocardial reperfusion and sepsis. Vascular endothelium plays an important role in the mechanism of stem cell therapy to regulate systemic inflammation and subsequent organ dysfunction. We evaluated how and whether bone marrow derived mononuclear cells (BMMNCs) could attenuate systemic inflammatory response in rat heatstroke model. By transplantation of BMMNCs, 1) the serum levels of inflammatory mediators and markers for endothelial injury were reduced, 2) lung edema and alveolar injury were attenuated, 3) damage of vascular endothelial glycocalyx layer was regulated, and 4) 7-Days mortality was significantly reduced. Our findings suggested that transplantation of BMMNCs attenuated acute systemic inflammation and vascular endothelial injury, reduced organ dysfunction, and improved survival in acute inflammation. Further investigations are required for the clinical application of bone marrow derived stem cell therapy.

Trauma is one of the leading causes of death worldwide. Recent development of surgical and intensive care could resuscitate the patients. Following the acute phase treatment, infectious complications become the most challenging problem in severely injured patients. To prevent and/or treat the infectious complications, we need to know the mechanisms of immune system homeostasis in these patients. Following severe injury, the immune system usually tends toward a pro-inflammatory phenotype and then changes to an anti-inflammatory phenotype. Injured tissue can be endogenous danger signals, and invited pathogens are exogenous danger signals. A combination of the endogenous and the exogenous signals trigger our immune system following injuries. The primed innate immune system is prepared for a rapid and strong antimicrobial immune defense. Injury also augments regulatory T cell activity, which can control the excess inflammatory response for trauma. The inflammatory response and the counter-inflammatory response protect the host in harmony. Disruption of the homeostasis leads the injured host to the worst outcome. We reviewed the mechanisms of the harmony and disruption of immune system homeostasis following injuries.

【Objective】 Paucity of Japanese literature on recurrent Clostridioides difficile infection (CDI) prompted investigation on risk in outpatients and inpatients using antimicrobial use density (AUD). 【Methods】 Recurrence was defined as diarrhea and positive toxin test (CDT) on 29 days or after CDI. Subjects were outpatients and inpatients in 10 wards 2007 through 2018. We analyzed statistics for CDT and CDI recurrence. We defined recurrence density, for which regression analysis was made for AUD. The internal review board approved ethics. 【Results】 In a total of 2,358 CDTs, 301 CDI patients, 22 recurrent patients (7.3％), outpatient units had 3 patients (0.9％) and the surgical ward had 6 patients (0.9％) without significant difference. For recurrence density in inpatients, AUDs of ampicillin/sulbactam, ceftazidime, meropenem, and piperacillin/tazobactam were significant (P＜0.05). 【Conclusion】 Outpatients with diarrhea need differential diagnosis of CDI. Surgical wards run risk of CDI as do broadspectrum antimicrobials, thus indicating intervention.

Clostridioides difficile infection (CDI) is a serious medical issue. Even though CDI can particularly be a problem when it occurs postoperatively, its occurrence following cardiovascular surgery remains to be investigated in Japan. The purpose of this study was to investigate CDI following cardiovascular surgery at Sendai Kosei Hospital. Postoperative CDI during the 5-year period spanning January 2013 to December 2017 was investigated. Overall morbidity due to postoperative CDI in patients in the cardiovascular surgery department was significantly lower than that among those hospitalized in the others (35/63,342 versus 659/778,017，P=0.01). The time to development of CDI tended to be shorter in patients with extracorporeal circulation and those undergoing Y-graft substitution procedures. Multicenter investigations employing larger patient samples are needed to clarify the status of CDI after cardiovascular surgery.

【Background】 The incidence of Clostridioides difficile infection (CDI) after orthopedic surgery is generally low. But, once they get infected, their risk of death will be high, and will increase length of stay and medical costs. 【Patients and Methods】 We explored cases that developed postoperative CDI among patients who received orthopedic surgery at our hospital from April 2016 to March 2019. 【Results】 Four cases (0.071％) developed CDI among 5,619 patients who received orthopedic surgery. All CDI patients received cefazolin as their antimicrobial prophylaxis (AMP), and only 1 patient received prolonged administration of 19 days. Two received additional antibiotics after surgery, three had multiple co-morbidities, and two were hospitalized before surgery for more than 11 days. All patients received oral metronidazole (MNZ) for treatment, but 1 case required intravenous MNZ with oral vancomycin (VCM) as there was no improvement. 【Discussion】 Age, comorbidity, length of stay before surgery, and administration of multiple antibiotics and prolonged duration are the risk factors of CDI in orthopedic surgery. These factors may have influenced the onset of CDIs. AMP is one of the CDI risk factor which can be modified easily, and its adequate use may also improve CDI risk. We believe it is important not to administer AMP too long, especially in institutions with high CDI incidence.

Solid organ transplantations have led to high frequency of Clostridioides difficile infections (CDIs). In patients with kidney transplantation, the frequency of CDI has been lower than those with other solid organ transplantations, such as liver, heart or pancreas transplantations. The episode of CDIs mostly have been reported within one month after any transplantations. Age, antimicrobials or immunosuppressants might be highly associated with CDIs. Since the incidences of relapsed CDI have reported to be 29-50％ in patients with heart or lung transplantations, prophylactic administration with VCM or fecal microbial transplantation therapy has been studied against those patients.