Impact on Antifungal Susceptibility Patterns of Previous vs. Revised Clinical and Laboratory Standards Institute Breakpoints for Candida Species Isolated from Candidemia: Experience of Two Tertiary Care Institutions in Japan.

BACKGROUND: Candidemia has a high mortality rate. Identifying prognostic factors of candidemia, based on each regional data, is essential for better management. The Clinical and Laboratory Standards Institute (CLSI) recently revised Candida species-specific breakpoints (R-BP) for antifungal agents. Few studies have investigated the detection performance of resistance in Candida species by comparing the R-BP and previous species non-specific CLSI breakpoint (P-BP) among patients with candidemia. The primary objective was to investigate the impact of the R-BP on the antifungal susceptibility patterns of Candida species, while the secondary objective was to identify the prognostic factors of candidemia. METHODS: A total of 193 Candida species isolated from 187 patients with candidemia between January 2007 and December 2016 were examined. Susceptibility based on CLSI M27-A3 was defined as the P-BP and based on species-specific CLSI M59 or M60 breakpoint was defined as the R-BP. Multivariate Cox's hazard analysis was performed to identify prognostic factors within 30 days of the diagnosis of candidemia. RESULTS: A significant difference was observed in the susceptibility rate to fluconazole (FLCZ) (P-BP; 93.0% vs. R-BP; 79.4%) and to voriconazole (VRCZ) (P-BP; 97.2% vs. R-BP; 91.0%). The susceptibilities of C. parapsilosis, C. glabrata, and C. tropicalis to azole antifungal agents were markedly lower with the R-BP. Based on the R-BP, anti-fungal therapy was regarded as inappropriate for approximately 10% of the patients. The 30-day mortality rate was 29.4%. In a multivariate Cox's hazard analysis, age, lung disease, C. albicans, and the absence of antifungal therapy were associated with a high mortality rate, whereas serum albumin, C. parapsilosis, surgical wards, the removal of central venous catheter (CVC), and follow-up blood culture tests to confirm the clearance of Candida species were associated with a lower mortality rate. CONCLUSIONS: Early initiation of antifungal therapy, removal of CVC, and follow-up blood culture tests are essential for improving the outcome. The R-BP efficiently detected non-susceptible strains to FLCZ and VRCZ, particularly in non-albicans Candida species. The present results support the importance of antifungal susceptibility tests and interpretations based on the R-BP among patients with candidemia.

[Problems in the management of clinical laboratories in Japan].

In Japan, laboratory automation has spread over the last two decades. Laboratory automation has saved time and labor for routine sample tests in clinical laboratories, and contributed to the downsizing of the division. This "contribution" resulted in re-arrangement of the work-force, namely, shrinkage of the blood chemistry division and expansion of the physiological tests and diagnostic imaging division. Some may call this re-arrangement as an adaptation for survival. However, I am concerned that extreme adaptation may cause irreversible shrinkage of clinical laboratories and laboratory medicine itself. In fact, outsourcing of sample tests including microbiological tests has become very popular over the last decade. Since the cost for microbiological tests is suppressed by the national health insurance policy, it is becoming difficult to keep microbiological laboratories in small-scale hospitals. The presence of a microbiological laboratory in a hospital is crucial for prompt and appropriate therapies for infectious diseases, and is essential for advanced infection control activities. The government is pushing forward fixed-term employment in national universities and hospitals, threatening long-term career planning for medical technologists. We have to keep in mind that nurturing medical personnel with special skills and extensive knowledge is mandatory to university hospitals, and laboratory medicine is crucial to the progress of modern medicine.

Docosahexaenoic acid exerts anti-inflammatory action on human eosinophils through peroxisome proliferator-activated receptor-independent mechanisms.

BACKGROUND: Despite the fact that previous studies have indicated the significant roles of polyunsaturated fatty acids (PUFAs) in the immune system through peroxisome proliferator-activated receptor alpha (PPARα) and PPARγ, the biological functions and the mechanisms of action in eosinophils are poorly understood. METHODS: We investigated the functional effects of docosahexaenoic acid (DHA, n-3 PUFA) on human peripheral blood eosinophils, using in vitro systems to test the hypothesis that DHA negatively regulates eosinophil mechanisms through PPARα and PPARγ. RESULTS: Eosinophil apoptosis that spontaneously occurs under normal culture conditions was accelerated in the presence of DHA. In addition, eotaxin-directed eosinophil chemotactic responses were inhibited by pretreatment with DHA, disturbing both the velocity and the directionality of the cell movement. Pharmacological manipulations with specific antagonists indicated that the effects of DHA were not mediated through PPARα and PPARγ, despite the presence of these nuclear receptors. DHA also induced Fas receptor expression and caspase-3 activation that appears to be associated with a proapoptotic effect of DHA. Further, DHA rapidly inhibited the expression of eotaxin receptor C-C chemokine receptor 3 and eotaxin-induced calcium influx and phosphorylation of extracellular signal-regulated kinase. Interestingly, these inhibitory effects were not observed with linoleic acid (n-6 PUFA). CONCLUSIONS: The data might explain one of the mechanisms found in previous research showing the favorable effects of n-3 PUFA supplementation on allergic diseases, and provide novel therapeutic strategies to treat eosinophilic disorders.

[Physiopathological evaluation of defecatory problems in elderly people using saline enema test and fecoflowmetry].

The population of the aged people is increasing rapidly in developed countries. Bowel care is recognized as an important factor to the wellbeing of the disabled elderly people. To evaluate the physiopathology of defecatory problems in the elderly, we applied saline enema test and fecoflowmetry; that is, pressure fluctuations of the rectum and anal canal were simultaneously recorded during saline infusion in the rectum, and then the saline evacuation curve was recorded in the elderly subjects. The patterns of the pressure fluctuations in the rectum and anal canal were analyzed in saline enema test. In fecoflowmetry, the shape of the evacuation curve and several parameters such as, flow rate and evacuation time were evaluated. The saline volume required to elicit rectal contractions and relaxations of the anal canal were significantly decreased in the patients with the lesions narrowing the spinal canal. The shape of evacuation curve represented the state of defecation in each subject. Subjects without defecatory problems had high flow rates and short evacuation time, while subjects with incontinence and/or constipation had low flow rates and long evacuation time. Furthermore, big and slow periodic pressure fluctuations of the anal canal, so called ultra slow waves, were seen in some patients with severe chronic constipation accompanying megacolon. These findings suggested that the physiopathology of defecatory problems in the elderly is variable and complicated, and that the appropriate treatment for these patients is achieved through appropriate evaluation.

Evaluation of anorectal function in patients with tethered cord syndrome: saline enema test and fecoflowmetry.

OBJECT: Disturbance in anorectal function is a major factor restricting the activities of daily living in patients with spinal cord disorders. To detect changes in anorectal motilities due to a tethered spinal cord, anorectal functions were evaluated using a saline enema test and fecoflowmetry before and after patients underwent untethering surgery. METHODS: The bowel functions in five patients with a tethered cord syndrome (TCS) were evaluated by performing a saline enema test and fecoflowmetry. The contractile activity of the rectum, the volume of infused saline tolerated in the rectum, anal canal pressure, and the ability to evacuate rectal content were examined. The characteristic findings in anorectal motility studies conducted in patients with TCS were a hyperactive rectum, diminished rectal saline-retention ability, and diminished maximal flow in saline evacuation. A hyperactive rectum was considered to be a major contributing factor to fecal incontinence. In one asymptomatic patient diminished anal squeezing pressure was exhibited and was incontinent to liquid preoperatively, but recovered after surgery. Two patients who underwent surgery for myeloschisis as infants complained of progressive fecal incontinence when they became adolescents. In one patient fecal incontinence improved but in another patient no improvement was observed after untethering surgery. CONCLUSIONS: Fecodynamic studies allow the detection of neurogenic disturbances of the anorectum in symptomatic and also in asymptomatic patients with TCS. More attention should be paid to the anorectal functions of patients with TCS.

Evaluation of anorectal functions of children with anorectal malformations using fecoflowmetry.

BACKGROUND/PURPOSE: A simple and objective method evaluating the bowel functions of patients with anorectal anomalies is necessary. The authors applied fecoflowmetry and saline enama test for patients with anorectal anomalies to evaluate the fecodynamics and anorectal motilities in these children. METHODS: The bowel functions of 16 patients who underwent repair for anorectal malformations and 5 normal controls were evaluated by saline enema test and fecoflowmetry. The correlations between the clinical scores for the bowel functions and the parameters in fecodynamic studies were investigated. RESULTS: Seven of 16 patients exhibited periodical contractions of the rectum synchronized with relaxations of the anal canal during saline infusion as did the controls and had significantly higher clinical scores than the other patients. Two patients with severe chronic constipation lacked rectal contractions. Among the fecoflowmetric parameters, the maximum flow, average flow, and tolerable volume of saline infused into the rectum were significantly lower in the patients with low clinical scores than those of the controls. The maximal squeeze pressure and resting anal pressure were not significantly different between the patients and controls. CONCLUSION: Fecodynamic studies, such as fecoflowmetry and saline enema test, help in obtaining clinical indicators for the bowel functions of patients with anorectal anomalies.