There has been much progress in elucidation of the pathophysiology of severe sepsis / septic shock. Now it is widely accepted that fundamental process of severe sepsis / septic shock is the cytokine production through intracellular signal transduction activated by both pathogen-associated molecular patterns (PAMPS) and alarmin through pattern recognition receptors such as toll-like receptors. And it is also widely accepted that pro-inflammatory and anti-inflammatory hypercytokinemia plays a pivotal role in the pathophysiology of sepsis. As for cell death which is an important pathophysiological feature of sepsis-induced organ failure, recently autophagy becomes main target of the research even though anoxic necrosis and apoptosis drew attentions in the past decades. Genetic polymorphisms are also very important issue in elucidation of the pathophysiology of sepsis, because, an individual with cytokine- and innate immunity -related genetic polymorphisms shows severer inflammatory response to infectious insult, and shows less effectiveness to certain therapeutic approaches compared to septic patients without such genetic polymorphisms. Immunoparalysis is also important issue in the pathophysiology of severe sepsis and septic shock, since it is an important causative factor of serious superimposing infectious complication in the clinical course of sepsis. As for the treatment of severe sepsis / septic shock, Surviving Sepsis Campaign guidelines (SSCG) has gained popularity all over the world and has been applied in many ICU's even in Japan. However, there are some problems when we apply SSCG in our country. First, there are no descriptions on the countermeasures against hypercytokinemia even though it is now widely accepted that hypercytokinemia plays a pivotal role in the pathophysiology of severe sepsis / septic shock as mentioned above. Second, the majority of the therapeutic recommendations in SSCG are supported by the evidence gained by the randomized controlled trial on Caucasian populations who have different distribution of genetic polymorphisms compared to Japanese. We applied continuous hemodiafiltration with a cytokine-adsorbing hemofilter as countermeasure against hypercytokinemia and placed it as a mainstay of therapeutic approach to severe sepsis / septic shock. And we achieved excellent outcome with this therapeutic strategy compared to the outcome in previous reports from foreign countries. In future we should apply micro-RNA analysis to elucidate pathophysiology more precisely and stem cell therapy should be considered for the better survival and/or intact survival of severe sepsis / septic shock patients.

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The objective of this research is to reveal the influence of chronic psychosomatic stress such as night work by measuring the diurnal variation of salivary amylase activity (SAA). Fourteen medical providers who engaged in 24-hour uninterrupted service consisting of daytime and night-time duties in the emergency department were enrolled as the subjects. Diurnal variations over 2 days including a workday and a holiday were measured three times in a month for each subject. Salivary amylase activities were measured 7 times over these 2 days. Diurnal variations showed SAA increased from the morning to before evening meal and decreased until the next morning, which can be described as a convex curve in both workday and holiday. Dynamic programming method was used to compare a similarity of two curves. The similarity between workday and holiday curves was 0.72, suggesting that phase and shape between the two mean curves was changed. The similarities of medical doctor and paramedical staff were 0.94 of workdays and 0.93 of holiday, showing high similarity without being dependent on the day. The similarity between each individual and mean diurnal variation was 0.34±0.57 in a workday and 0.43±0.50 on a holiday, which suggested that the diurnal variations of SAA showed highly individual. Our results revealed that the hard nocturnal work is possibly reflected in the diurnal variations of SAA not depending on a difference in occupation.

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As the installation rate of automated external defibrillators (AEDs) increases, the more the opportunities doctors will have to operate on AEDs in hospitals. We examined the data of two cases in which patients were not deliverd shock by AEDs, although the doctors recognized the ventricular tachycardia (VT) on the monitor. Case one was a 78-year-old man who had been on admission for examination of a prostate tumor. He had a sudden cardiopulmonary arrest (CPA). AED monitor had shown VT but the heart rate was too slow to be an indication for shock. Case two was a 56-year-old woman who had received chemotherapy on admisson and had sudden CPA. The AED monitor had shown VT and prepared to deliver shock. At this point the amplitude quickly decreased and become asystole therefore no shock were delivered. The recommendation of American Heart Association and Association for the Advancement of Medical Instrumentation attached much more importance to specificity rather than sensitivity in judgement of shock indication by AED. This was to avoid inadequate shock and to insure the safe use by minimally trained personnel. Doctors should recognize limitations of the various types of AEDs and should consider preparing a standard defibrillator during cardiopulmonary resuscitation.

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A case of reversible pontine ischemia following diagnostic cerebral angiography performed to evaluate vertebral artery dissection (VAD) of ischemic onset is reported. A 40-year-old man presented with sudden neck pain, dizziness, difficulty in swallowing, and numbness in the left arm. Neurologically, his symptoms were compatible with incomplete Wallenberg syndrome. Diffusion-weighted magnetic resonance imaging (DWI) revealed a small infarction in the medulla oblongata, and the right VA was irregularly stenotic on magnetic resonance angiography (MRA). We suspected that the right VAD was the cause of the medullary infarction. Following conservative treatment, his deficits resolved quickly despite progression of the VAD as revealed by follow-up MRA. Subsequently, diagnostic cerebral angiography was performed with the purpose of evaluating the patency of the right VA and possibility of a dissecting aneurysm. Despite a seemingly uneventful procedure, however, the patient developed altered mental status and right-sided hemiparesis shortly after the placement of an angiographic catheter into the intact left VA. DWI obtained two hours after the procedure revealed a high-intensity signal in the paramedian pons. Following administration of IV heparin and edaravone, the neurological deficits as well as the high-intensity signal disappeared within 24 h. The patient was discharged without deficits 4 weeks after onset. Although cerebral angiography has been considered the gold standard for the diagnosis of VAD, its role in VAD of ischemic onset has recently been questioned, in light of its relatively benign natural history, improved quality of less invasive imaging modalities, and risks of cerebral angiography. From the perspective of avoiding complications, the common practice of obtaining diagnostic cerebral angiography from every patient with VAD of ischemic onset may have to be reviewed, and decision to perform cerebral angiography for those who have already been diagnosed with less invasive imaging modalities should be made cautiously and on case-by-case basis.

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A 51-year-old woman was admitted to our hospital because of anorexia and was diagnosed with gastric malignant lymphoma (diffuse large B-cell lymphoma) from the results of a gastric endoscopic examination. Abdominal CT scan detected a huge gastric tumor, with the maximum diameter of 21 cm, and swollen regional lymph nodes. During further examinations, she suddenly developed massive hematemesis, resulted in hemorrhagic shock. After blood transfusion improved her general condition, emergency endoscopic hemostasis was attempted, but was unsuccessful. Therefore, emergency operation was performed 13 hours after hematemesis. During laparotomy, a huge tumor was found to originate from the lesser curvature of the whole stomach and to invade the pancreas. Because of severe bleeding of the tumor, lymph node dissection was judged hazardous. Therefore, the primary tumor was resected by total gastrectomy (D0, retro-colic Roux-en Y reconstruction). The dimensions of the resected specimen weighing 2320 g were 25×14×9 cm. The clinical stage of the disease was II 1E (pancreas). Her postoperative clinical course was uneventful, and she was transferred to the Department of Internal Medicine for chemotherapy 14 days after the operation. At present, i.e., 2 years after the operation, she is alive with complete remission of the disease.

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