Usefulness of presepsin / creatinine ratio as a new index that corrects for renal function.

Background : Presepsin (P-SEP) is a highly specific sepsis marker, and its fluctuation with respect to advanced renal impairment or sample agitation has not been fully investigated. We evaluated several renal function-corrected P-SEP indices to establish a simple index and its reference range. Methods : Blood samples for P-SEP measurement were collected with minimal agitation. P-SEP levels were measured using the rapid automated immunoanalyzer "PATHFAST." This study included 85 chronic kidney disease (CKD) patients, 65 healthy volunteers, and 4 sepsis patients. Results : Patients stratified by estimated glomerular filtration rate (GFR) had significantly higher P-SEP levels for CKD stage G3, especially the advanced GFR stage. We evaluated presepsin / creatinine (P-SEP / CRE) and P-SEP / eGFR ratios as possible indices for renal function. The P-SEP / CRE ratio exhibited no increase correlating with the GFR stage and was identical in the normal and CKD groups ;  P-SEP / eGFR decreased if GFR stage worsened. The P-SEP / CRE ratio became significantly higher in sepsis patients and was a more useful index with a reference range of 67-263. Conclusions : P-SEP levels were inversely correlated with renal function, indicating the necessity to consider the influence of renal impairment in CKD patients. The P-SEP / CRE ratio is helpful for sepsis diagnosis, even in patients with renal impairment. J. Med. Invest. 68 : 105-111, February, 2021.

Clinical evaluation of presepsin considering renal function.

Presepsin, a glycoprotein produced during bacterial phagocytosis, is used as a sepsis marker for bacterial infections. However, presepsin levels are affected by renal function, and the evaluation criteria according to kidney function or in chronic kidney diseases remain controversial. Furthermore, presepsin may be increased by sample stirring, but no studies have evaluated this effect.In this study, we excluded the effect of stirring by standardizing the blood collection conditions, analyzed the influence of kidney function on presepsin concentrations, and recalculated the reference range based on the findings. EDTA-whole blood from 47 healthy subjects and 85 patients with chronic kidney disease was collected to measure presepsin by PATHFAST. Presepsin was found to be significantly correlated with the levels of creatinine (r = 0.834), eGFRcreat (r = 0.837), cystatin-C (r = 0.845), and eGFRcys (r = 0.879). Furthermore, in patients with CKD, presepsin levels stratified by eGFRcys showed a significant increase in the CKD G2 patient group and with advancing glomerular filtration rate stage. The following values were obtained: Normal: 97.6 ± 27.4 pg/mL, CKD G1: 100.2 ± 27.6 pg/mL, CKD G2: 129.7 ± 40.7 pg/mL, CKD G3: 208.1 ± 70.2 pg/mL, CKD G4: 320.2 ± 170.1 pg/mL, CKD G5: 712.8 ± 336.3 pg/mL. The reference range, calculated by a nonparametric method using 67 cases of healthy volunteers and patients with chronic kidney disease G1, was found to be 59-153 pg/mL, which was notably lower than the standard reference range currently used. Presepsin concentrations were positively correlated with a few biomarkers of renal function, indicating the necessity to consider the effect of renal function in patients with renal impairment. Using the recalculated reference range considering kidney function may improve the accuracy of evaluating presepsin for diagnosis of sepsis compared to the standard reference currently in use.

Donor quality of life in living-donor lobar lung transplantation.

BACKGROUND: Living-donor lobar lung transplantation has been established as a life-saving option for end-stage pulmonary diseases. However, factors associated with quality of life (QOL) of living lung donors have not been fully investigated. METHODS: A cross-sectional study was performed at Okayama University using the version 2 questionnaire of the 36-item Short Form (SF-36) Health Survey. Linear regression analysis was used to estimate the relationship of donor factors and recipient outcomes using the SF-36 component summary scores. RESULTS: Of 65 donors, 42 (65%) agreed to participate in this study; the mean age was 42 ± 1 (range 25 to 59) years. Mean time from the operation to questionnaire was 39 ± 4 (range 1 to 78) months. Donor-recipient relationships were as follows: sibling (18 cases); spouse (9 cases); parent (11 cases); and child (4 cases). Thirty-four of 42 donors were paired with those who donated their organ to the same recipient. Both physical and mental health scores in donors were higher than those in the general Japanese population. Lower mental health scores were seen in those who donated to their child or parent. There was a significant correlation in mental health scores between the paired donors. In the univariate analysis, donor age (r = -0.35, p = 0.02), donor-recipient relationship (r = 0.38, p = 0.01) and recipient death (r = -0.42, p = 0.006) were factors significantly associated with donor mental health scores. CONCLUSIONS: The average QOL in the living lung donors was better than that of the general population. However, a fatal outcome in the recipient significantly impacted donor mental health QOL. Ensuring that donor candidates consider both the risks/benefits of donation, and the potential recipient outcomes may be critical in the informed consent process.

Nerve sheath myxoma (neurothekeoma) arising in the oral cavity: histological and immunohistochemical features of 3 cases.

This report describes the histological and immunohistochemical characteristics of 3 cases of nerve sheath myxoma (NSM)/neurothekeoma arising in the oral cavity. Histopathologically, 3 distinct variants were observed based on the amount of myxoid matrix: classic/hypocellular, cellular, and mixed types. Immunohistochemically, all types expressed strong immunoreactivity to S-100 protein (3/3), NSE (neuron-specific enolase) (3/3), and NGFR (nerve growth factor receptor) (3/3), whereas all cases were negative for SMA (smooth muscle actin) and FVIII. The number of Ki-67 positive cells was less than 5% in all lesions confirming the slow growing characteristics of NSM. The results suggest that NSMs of the oral cavity are true peripheral nerve sheath tumors and show close relationship to schwannoma.

Altered expression of desmocollin 3, desmoglein 3, and beta-catenin in oral squamous cell carcinoma: correlation with lymph node metastasis and cell proliferation.

Desmocollin 3 (Dsc3) and desmoglein 3 (Dsg3) are both transmembrane glycoproteins that belong to the cadherin family of calcium-dependent cell adhesion molecules. beta-Catenin is a member of the cadherin-catenin complex that mediates homotypic cell-cell adhesion and is also an important molecule in the wnt signaling pathway. In this study, we examined the simultaneous expression level of Dsc3, Dsg3, and beta-catenin in oral squamous cell carcinomas (OSCCs) and normal oral epithelia using immunohistochemistry. There was a significant correlation (p < 0.05) among the following variables in OSCCs: reduced or loss of expression of Dsc3, Dsg3, and beta-catenin compared to normal oral epithelium, reduced or loss of expression of Dsc3 and histological grade (moderately or poorly differentiated), and reduced or loss of expression of beta-catenin and lymph node metastasis. Furthermore, a positive correlation was found between reduced or loss of beta-catenin staining and reduced or loss of Dsc3 staining in lymph node metastatic cancer tissue (r = 0.734, p < 0.05). These results suggest an abnormal expression of Dsc3, Dsg3, and beta-catenin induced in the progression of oral carcinomas and that the Dsc3 expression level might be related to the regulation of beta-catenin in lymph node metastasis and cell proliferation in OSCCs.

Activation of ERK1/2 and cyclin D1 expression in oral tongue squamous cell carcinomas: relationship between clinicopathological appearances and cell proliferation.

We report an immunohistochemical investigation of the expression of activated extracellular signal-regulated kinase (ERK1/2) and cyclin D1 protein in both oral tongue squamous cell carcinomas (OTSCCs) and normal tongue epithelium. The expression of Ki-67 labeling index (LI) was also examined in order to evaluate cell proliferation activity. The expression of activated ERK1/2, cyclin D1 protein and Ki-67 LI were significantly stronger in OTSCCs than in normal oral mucosa (P<0.05). Both over-expression of activated ERK1/2 and positive expression of Ki-67 in OTSCCs were significantly associated with a moderately or poorly differentiated grade of carcinoma (P<0.05). Cyclin D1 immunostaining showed statistically significant association with both lymph node metastasis (P<0.05) and a tumor thickness >5mm (P<0.05). Over-expression of activated ERK1/2 was positively correlated with cyclin D1 protein expression (P<0.05, r=0.624) and cell proliferation-related indexes Ki-67 (P<0.05, r=0.723). Our results suggest that over-expression of activated ERK1/2 and cyclin D1 protein are involved in oral tongue carcinogenesis, and that activation of ERK1/2 might be related to cell cycle regulation and cell proliferation in OTSCCs.