Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1-27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness. CASE PRESENTATION: A 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels. CONCLUSION: Herein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

Analysis of the diagnostic capabilities of urinary neutrophil gelatinase-associated lipocalin and serum procalcitonin for acute kidney injury at the early stage of critical care intensive care unit admission.

BACKGROUND: Acute kidney injury (AKI) is a disease that negatively affects patient prognosis and requires early diagnosis and treatment. Biomarkers that predict AKI are needed for early diagnosis of this disease. METHODS: We compared the AKI group and the non-AKI group in patients who were admitted to our critical care intensive care unit (ICU) and conducted a comparative study focusing on urinary neutrophil gelatinase-associated lipocalin (U-NGAL) and serum procalcitonin (PCT). RESULTS: Seventy-one out of 106 ICU inpatients were diagnosed with AKI in accordance with the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Among the patients who were diagnosed with AKI stages 1 to 3, 94.4% of all patients reached the maximum stage by day 5 after admission. Comparing the non-AKI group and AKI stage 1 to 3 on days 1 to 3 after admission, U-NGAL and PCT levels in the stage 3 group were significantly higher than those in the non-AKI group. Additionally, in receiver operating characteristic curve (ROC) analysis on days 1-3 after admission, U-NGAL and PCT levels can be used as biomarkers for the diagnosis of AKI, and in particular, AKI stage 3 can be predicted and diagnosed with high accuracy. U-NGAL and PCT levels were also significantly higher in AKI due to sepsis and acute pancreatitis and due to sepsis, respectively. CONCLUSIONS: Measuring U-NGAL and PCT levels as biomarkers for AKI may further improve the accuracy of AKI diagnosis in critical care ICU.

Apolipoprotein E-related glomerular disorders.

Of the glomerular disorders that occur due to apolipoprotein E (apoE) mutations, apoE2 homozygote glomerulopathy and lipoprotein glomerulopathy (LPG) have been characterized. ApoE2 homozygote glomerulopathy has been found in individuals expressing homozygous apoE2/2. This was characterized histologically by glomerulosclerosis with marked infiltration of foam cells derived from macrophages, and occasionally with non-lamellated lipoprotein thrombi. Recently, several cases of apoE Toyonaka (Ser197Cys) combined with homozygous apoE2/2 have been reported, in which non-immune membranous nephropathy-like features were observed in glomeruli. Interestingly, in these cases, apoE accumulation was identified by tandem mass spectrometry. Therefore, it is speculated that these findings may arise from apoE molecules without lipids, which result from hinge damage by apoE Toyonaka and may cross the glomerular basement membrane as small molecules. LPG is primarily associated with heterozygous apoE mutations surrounding the low-density lipoprotein-receptor binding site, and it is histologically characterized by lamellated lipoprotein thrombi that lack foam cells. Recent studies have suggested that LPG can be induced by thermodynamic destabilization, hydrophobic surface exposure, and the aggregation of apoE resulting from the incompatibility of apoE mutated residues within helical regions. Additionally, apoE5 may play a supporting role in the development of LPG and in lipid-induced kidney diseases via hyperlipoproteinemia. Thus, it is interesting that many apoE mutations contribute to characteristic glomerular disorders through various mechanisms. In particular, macrophages may uptake lipoproteins into the cytoplasm and contribute to the development of apoE2 homozygote glomerulopathy as foam cells, and their dysfunction may contribute to the accumulation of lipoproteins in the glomerulus, causing lipoprotein thrombi in LPG.

Correction to: Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.

In the Original publication of the article, the legend appearing inside the flow chart has been incorrectly published.

Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.

There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5 mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10 mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5 mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; - 7.9 mmHg vs. + 2.7 mmHg; p = 0.0002, diastolic BP; - 3.9 mmHg vs. + 0.6 mmHg; p = 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.

Evaluation of the Time-Dependent Changes and the Vulnerability of Carotid Plaques Using Contrast-Enhanced Carotid Ultrasonography.

BACKGROUND: The association of carotid plaque enhancement on contrast-enhanced carotid ultrasound (CEUS) and plaque vulnerability evaluated by magnetic resonance imaging (MRI) was to be determined. MATERIALS AND METHODS: The 103 patients underwent CEUS from May 2013 until June 2016. CEUS images of the carotid plaque were obtained offline. Plaque images obtained at 1, 3, 5, and 10 minutes were compared with the reference image, defined as the image obtained at 0 minute. Plaque brightness was assessed using the gray-scale median during contrast enhancement (GSM-C). Plaque vulnerability was evaluated using T1- and T2-weighted MRI and Volume ISotropic TSE Acquisition (VISTA), with a VISTA cutoff value for the plaque muscle ratio (PMR) of 1.5. Time-dependent changes in the GSM-C were evaluated, and those between 0 and 1 minute were compared with the PMR values determined on MRI. FINDINGS: GSM-C decreased significantly over time, from 32.0 at 0 minute to 28.0 at 1 minute, 25.0 at 3 minutes, and 19.0 at 10 minutes. The greater the increase in the changes in the GSM-C from 0 to 1 minute, the more significant the association with a PMR higher than the median on T1 (GSM-C: 0 minute: 29.0, 1 minute: 24.0, P = .015), a PMR less than or equal to the median on T2 (0 min: 35.0, 1 min: 28.0, P = .003), and a PMR more than 1.5 determined on VISTA (GSM-C: 0 minute: 29.0, 1 minute: 24.0, P = .005). CONCLUSIONS: Early changes in the GSM-C evaluated with CEUS indicate significant plaque vulnerability on MRI.

BK-UM in patients with recurrent ovarian cancer or peritoneal cancer: a first-in-human phase-I study.

BACKGROUND: BK-UM (CRM197) is a mutant form of diphtheria toxin and a specific inhibitor of heparin-binding epidermal growth factor-like growth factor (HB-EGF). We assessed the safety, pharmacokinetics, recommended dose, and efficacy of BK-UM in patients with recurrent ovarian cancer (OC) or peritoneal cancer (PC), and measured HB-EGF levels in serum and abdominal fluid after BK-UM administration. METHODS: Eleven patients with advanced or recurrent OC or PC were enrolled and treated with BK-UM via the intraperitoneal route. The dose was escalated (1.0, 2.0, 3.3, and 5.0 mg/m2) using a 3 + 3 design. RESULTS: Eight of 11 patients completed treatment. No dose-limiting toxicity (DLT) was experienced at dose levels 1 (1.0 mg/m2) and 2 (2.0 mg/m2). Grade 3 transient hypotension as an adverse event (defined as a DLT in the present study) was observed in two of four patients at dose level 3 (3.3 mg/m2). Treatment with BK-UM was associated with decreases in HB-EGF levels in serum and abdominal fluid in seven of 11 patients and five of eight patients, respectively. Clinical outcomes included a partial response in one patient, stable disease in five patients, and progressive disease in five patients. CONCLUSIONS: BK-UM was well tolerated at doses of 1.0 and 2.0 mg/m2, with evidence for clinical efficacy in patients with recurrent OC or PC. A dose of 2.0 mg/m2 BK-UM is recommended for subsequent clinical trials. TRIAL REGISTRATION: This trial was prospectively performed as an investigator-initiated clinical trial. The trial numbers are UMIN000001002 and UMIN000001001, with registration dates of 1/30/2008 and 2/4/2008, respectively. UMIN000001001 was registered as a trial for the continuous administration of BK-UM after UMIN000001002 .

[Analysis of Hepatitis B Virus Reactivation in Fukuoka University Hospital].

Immunosuppressive therapy or chemotherapy-induced hepatitis B virus (HBV) reactivation can cause se- vere hepatitis in inactive HBV carriers or patients with resolved infection. We surveyed patients with measured HBV DNA levels from 2009 to 2014, and analyzed the clinical profile, treatment regimen and the period leading up to HBV reactivation from therapy start date. Between 2009 and 2014, the total number of HBV viral load measurements taken in our hospital increased 2.3-fold. HBV DNA measurements requested by the Department of Gastroenterology and Hepatology ac- counted for 82.8% of the total in 2009; however, this was reduced to 38.0% in 2014, as the number of re- quests from other departments increased. We referred all patients with reactivated HBV infection to a hepatology specialist. The total number of reactivation patients in 2014 was increased to about 8.2 times that observed in 2009. Nineteen males and 24 females were included in our cohort, and the average age was 69±10.1 years old. Thirty-two patients had previously received chemotherapy, and seven had undergone immunosuppressive treatment. A delay of more than 12 months from commencement of therapy to HBV reactivation was observed in 49% of patients. These results indicate that it is very important to monitor HBV DNA and properly enforce pre-treatment examinations according to the guidelines for prevention and treatment of HBV during immunosuppressive therapy. [Original].

End-stage renal disease in Japanese children: a nationwide survey during 2006-2011.

BACKGROUND: End-stage renal disease (ESRD) in children is considered a rare, but serious condition. Epidemiological and demographic information on pediatric ESRD patients around the world is important to better understand this disease and to improve patient care. The Japanese Society for Pediatric Nephrology (JSPN) reported epidemiological and demographic data in 1998. Since then, however, there has been no nationwide survey on Japanese children with ESRD. METHODS: The JSPN conducted a cross-sectional nationwide survey in 2012 to update information on the incidence, primary renal disease, initial treatment modalities, and survival in pediatric Japanese patients with ESRD aged less than 20 years during the period 2006-2011. RESULTS: The average incidence of ESRD was 4.0 per million age-related population. Congenital anomalies of the kidney and urinary tract were the most common cause of ESRD, present in 39.8 % of these patients. In addition, 12.2 % had focal segmental glomerulosclerosis and 5.9 % had glomerulonephritis. Initial treatment modalities in patients who commenced renal replacement therapy (RRT) consisted of peritoneal dialysis, hemodialysis, and pre-emptive transplantation (Tx) in 61.7, 16.0, and 22.3 %, respectively. The Japanese RRT mortality rate was 18.2 deaths per 1000 person-years of observation. CONCLUSION: The incidence of ESRD is lower in Japanese children than in children of other high-income countries. Since 1998, notably, there has been a marked increase in pre-emptive Tx as an initial treatment modality for Japanese children with ESRD.

Effective method of continuous rocuronium administration based on effect-site concentrations using a pharmacokinetic/pharmacodynamic model during propofol-remifentanil anesthesia.

BACKGROUND: Rocuronium bromide (Rb) is a rapid onset, intermediate-acting neuromuscular blocking agent that is suitable for continuous administration. The appropriate rate of rocuronium administration is, however, difficult to determine due to large interindividual differences in sensitivity to rocuronium. The aim of this study was to clarify whether the simulated rocuronium concentration at the time of recovery to %T1 > 0 % after the initial administration of rocuronium is a good indicator of optimal effect-site concentrations during continuous rocuronium administration. METHODS: Twenty-one patients were anesthetized with propofol. After induction, Rb 0.6 mg/kg was administered intravenously, and nerve stimulation using the single stimulation mode was conducted every 15 s. When %T1 recovered to >0 % after the initial administration of Rb, the effect-site concentration of rocuronium, calculated by pharmacokinetic simulation with Wierda's set of parameters, was recorded and defined as the recovery concentration (Rb r.c.). The administration rate of rocuronium was adjusted to maintain the Rb r.c. during surgery. Rb administration was discontinued just before the end of surgery, and the recovery time until %T1 > 25 % was recorded. Plasma Rb concentrations were measured at 1 and 3 h after the initiation of continuous Rb administration. RESULT: The mean Rb r.c. was 1.56 ± 0.35 µg/ml, with minimum and maximum values of 1.09 and 2.08 µg/ml, respectively. The %T1 did not increase above 10 % in any of the patients during continuous administration of Rb, and the recovery period to %T1 > 25 % ranged from 9 to 29 min. The effect-site concentrations of Rb calculated with Wierda's parameters significantly correlated with plasma concentrations (P < 0.01) at both 1 and 3 h after the initial administration of Rb. CONCLUSION: The results suggest that our method may be one of the most reliable protocols for the continuous administration of Rb described to date for maintaining suitable muscle relaxation during surgery without excessively prolonged effects.

A Hospital-Based Analysis in the Department of Clinical Chemistry for the Patients with HBV Reactivation after Anti-Cancer or Immunosuppressive Therapy.

OBJECTIVES: Anti-cancer and immunosuppressive drugs often induce hepatitis B virus (HBV) reactivation, resulting in lethal hepatitis in the worst cases. It is to elucidate the clinical characteristics of the patients in our hospital, who underwent HBV-related examinations to help prevent HBV-associated hepatitis by reactivation during the two-year period after the announcement of new guidelines by the Ministry of Health, Labour and Welfare of Japan in January 2009. STUDY DESIGN: We enrolled 811 patients who were examined for HBs antigen, anti-HBc antibody, anti-HBs antibody and HBV DNA regarding HBV reactivation. RESULTS: The underlying diseases were hematological malignancies, followed by various other cancers, rheumatoid arthritis, Crohn's disease, and so on. The patients in their 60s showed the peak in the age distribution. The positive ratio of anti-HBc antibody was higher over the age of 40. The rate of reactivation was 7.7% in HBV carriers and 2.0% in the HBV-resolved patients. HBV reactivation occurred in two HBV carriers and four HBV-resolved patients. The three patients, showing hepatitis were two HBV carriers and one HBV-resolved patient without monitoring of HBV DNA, because their therapies started before announcement of the guidelines. In other three patients with reactivation from HBV-resolved infections, HBV DNA returned under detection by immediate administration of entecavir without following hepatitis. CONCLUSION: The patients at high risk of HBV reactivation were prevented from HBV-related hepatitis only by following the guideline. The screening for such patients and monitoring HBV DNA in the guideline are requisite to prevent HBV-related hepatitis.

[The Effect of Remifentanil on the Estimated Target Effect-site Concentration (esTEC) of Propofol during Total Intravenous Anesthesia].

BACKGROUND: Using an algorithm by which the effect-site concentration of propofol (esTEC) necessary for BIS level set from information input from BIS monitor and TCI pump is estimated, the effect of remifentanil on esTEC was investigated. METHODS: In 14 abdominal/thoracic surgical patients managed under total intravenous anesthesia with propofol and remifetanil, the distribution of relation between the effect-site concentration of remifetanil and remifentanil esTEC was analyzed in a retrospective manner. RESULTS: While the propofol esTEC decreased in accordance with the increase of the effect-site concentration of remifetanil, the effect-site concentration of propofol esTEC45 for maintaining BIS 45 became within a certain range and with less dispersion when the concentration of remifetanil exceeded 10 ng x ml(-1). CONCLUSIONS: A mutual interaction was observed between propofol esTEC and remifetanil. For anesthetic management with less variation in BIS levels, it was considered that 10 ng x ml(-1) or higher of the effect-site concentration of remifetanil would be necessary.

Lipoprotein glomerulopathy may provide a key to unlock the puzzles of renal lipidosis.

Lipoprotein glomerulopathy is an inherited renal disease characterized by unique lipoprotein thrombi in the glomerulus and is associated with the APOE mutation. Hu and colleagues investigated the genetic and clinical features of a large group of patients with lipoprotein glomerulopathy who carried APOE Kyoto, a major APOE variant. Their findings suggest its descent through a founder effect. Fibrate therapy in this group showed favorable results in the patient and renal survival rates.

Apolipoprotein E mutations: a comparison between lipoprotein glomerulopathy and type III hyperlipoproteinemia.

Apolipoprotein E (ApoE) serves as a ligand for the low-density lipoprotein (LDL) receptor and cell surface receptors of the LDL receptor gene family. More than 10 different causative apoE mutations associated with lipoprotein glomerulopathy (LPG) have been reported. ApoE polymorphisms including three common phenotypes (E2, E3, E4), and a variety of rare mutations can affect blood cholesterol and triglyceride levels. The N-terminal domain of apoE is folded into a four-helix bundle of amphipathic α-helices, and contains the receptor-binding domain in which most apoE mutations that cause LPG or dominant mode of type III hyperlipoproteinemia (HL) are located. No single apoE mutation has been reported that causes both LPG and the dominant mode of type III HL.

Topics in lipoprotein glomerulopathy: an overview.

Here, we introduce four topics in lipoprotein glomerulopathy (LPG). To date, approximately 150 cases of LPG have been reported worldwide. Recently two groups studied hot spots of APOE-Sendai and APOE-Kyoto, the representative variants of LPG, in narrow areas of Japan and China, respectively. They suggest that both variants have descended through a founder effect. APOE-Sendai and APOE-Kyoto cause different transformations of apolipoproteins aggregating lipoproteins and resulting in lipoprotein thrombi within the glomerulus. Moreover, the macrophage impairment in LPG may provide another mechanism for lipoprotein thrombi in which massive lipoproteins accumulate in the glomerulus without foam cells. On the other hand, the administration of fibrate with the intensive control of triglyceride and apolipoprotein E particularly from the early phase will ameliorate LPG and prevent renal dysfunction.

Efficacy and safety of darbepoetin alfa for anemia in children with chronic kidney disease: a multicenter prospective study in Japan.

BACKGROUND: We evaluated the safety and efficacy of darbepoetin alfa (DA), an attractive alternative to recombinant human erythropoietin (rHuEPO) in managing renal anemia, in Japanese children with chronic kidney disease (CKD) on peritoneal dialysis (PD) and hemodialysis (HD), and not on dialysis (ND). METHODS: A total of 31 pediatric CKD patients (13 PD, 2 HD, and 16 ND) were enrolled. DA was administered bi-weekly intravenously (IV) or subcutaneously (SC) for PD or ND patients, and weekly IV for HD patients for 24 weeks. The target Hb was defined as 11.0 to ≤13.0 g/dl. In patients receiving rHuEPO, the initial DA dose was calculated at 1 µg DA for 200 IU rHuEPO. The initial DA dose for naïve patients was determined by body weight, and intended not to exceed 0.5 µg/kg per administration. For some PD or ND patients, the dosing frequency was subsequently changed to once every 4 weeks. RESULTS: Mean Hb values increased from 10.5 ± 1.1 to 11.1 ± 1.1 g/dl after 4 weeks of DA treatment. The target Hb was achieved in all patients, 64.5 % of whom maintained the value at completion of the study. Hb responses were similar between IV and SC. The dosing frequency was extended to once every 4 weeks in 37.9 % of PD or ND patients. Eighty-seven adverse events were noted in 27 (87.1 %) of 31 patients, none of which were associated with DA. CONCLUSION: These results suggest that IV or SC administration of DA is an effective and safe treatment for renal anemia in Japanese children with CKD.

Suspected intraoperative formation of left atrial thrombus in a patient with atrial fibrillation receiving bridging anticoagulation therapy.

We present a patient with atrial fibrillation (AF) in whom a left atrial (LA) thrombus might have formed during laparotomy despite bridging anticoagulation therapy. No evidence of thrombus was detected by transesophageal echocardiography (TEE) at the start of surgery; however, a thrombus measuring 13 × 10 mm was found in the LA appendage by the end of the procedure, suggesting that thrombus might develop intraoperatively in patients with AF even when bridging anticoagulation is properly established. Intraoperative TEE can assist in detecting intracardiac thrombus in patients with AF regardless of their anticoagulation status and provides a tool for intervention to prevent systemic embolization.

Perfusion index as a possible predictor for postanesthetic shivering.

BACKGROUND: Postanesthetic shivering can be triggered by surgical stress and several aspects of anesthetic management and is frequently preceded by a decrease in peripheral blood flow due to thermoregulatory vasoconstriction. As perfusion index correlates with peripheral blood flow, we examined whether perioperative perfusion index, measured using pulse oximetry, might be correlated with postanesthetic shivering. METHODS: Twenty-eight patients presenting for elective abdominal surgery were enrolled. Core (esophagus) and peripheral (finger) temperatures and perfusion index were recorded in the perioperative periods. Correlations between perfusion index and peripheral temperature and core-to-peripheral temperature gradient were then explored. Plasma levels of epinephrine and norepinephrine were also measured. The extent of shivering was graded after emergence from anesthesia. RESULTS: Perfusion index declined before emergence from anesthesia in patients who then developed postanesthetic shivering. This coincided with the time at which the difference between core and peripheral temperature became dissociated and peripheral temperature declined. Perioperative perfusion index was correlated with peripheral temperature and peripheral-core temperature gradient. Perfusion index at closure of the peritoneum predicted postanesthetic shivering and was significantly correlated with the extent of shivering. Plasma levels of both epinephrine and norepinephrine were significantly elevated after shivering events. CONCLUSIONS: Perfusion index was significantly lower in patients with postanesthetic shivering before emergence from anesthesia, indicating that measurement of perfusion index during and before the end of anesthesia might be a useful means of predicting postanesthetic shivering.

[Usefulness of Procalcitonin Measurement for the Detection of Sepsis].

Procalcitonin (PCT) is a frequently used marker for bacterial sepsis. The present study was aimed to assess the usefulness of PCT measurement in patient with sepsis. We studied the relationship between serum PCT level and blood culture in clinical 209 cases admitted from January 2010 through June 2010. We compared PCT level with blood culture results and other clinical data, and diagnosis such as sepsis and systemic inflammatory response syndrome (SIRS) were obtained from the medical records. In the case of patients with positive blood cultures and PCT < 0.5 ng/mL, the false- positive blood culture was suspected. The possibility of bacteremia was high when PCT level was more than 0.5 ng/mL. Patients with PCT ≥ 2 ng/mL had significant correlation with the presence of sepsis. The PCT measurement could be performed and reported rapidly and provided valuable information before availability of culture results. In this study, we found that the PCT would be a useful biomarker for confirming and ruling out sepsis.

A highly efficient catalytic method for the synthesis of phosphite diesters.

In contrast to conventional methods that rely on stoichiometric activation of phosphonylating reagents, we have developed a highly efficient catalytic method for the synthesis of phosphite diesters using a readily available phosphonylation reagent and alcohols with environmentally benign Zn(ii) catalysts. Two alcohols could be introduced consecutively on the P center with release of trifluoroethanol as the sole byproduct, without any additive, under mild conditions. The products could be oxidized smoothly to access phosphate triesters. A range of alcohols, including sterically demanding and highly functionalized alcohols such as carbohydrates and nucleosides, can be applied in this reaction.