Mortality risk factors and fulminant sub-phenotype in anaerobic bacteremia: a 10-year retrospective, multicenter, observational cohort study.

PURPOSE: During the last decade, the incidence of anaerobic bacteremia (AB) has been increasing. Patients with AB may develop complex underlying diseases, which can occasionally be accompanied by fatal or fulminant outcomes. However, the risk factors for AB-related mortality remain unclear. Herein, we sought to elucidate the risk factors for AB-related mortality. METHODS: In this multicenter, retrospective, observational study, we enrolled patients with culture-proven AB from six tertiary hospitals in Japan, between January 2012 and December 2021. Data on patient and infection characteristics, laboratory findings, treatment, and outcome were collected, and their associations with mortality were analyzed. RESULTS: A total of 520 participants were included. The 30-day mortality in the study cohort was 14.0% (73 patients), and malignant tumors were frequently observed comorbidities in 48% of the entire cohort. Multivariable logistic regression analysis showed a Charlson comorbidity score of > 6, serum creatinine level of > 1.17 mg/dL, and hypotension to be independent risk factors for 30-day mortality in AB (odds ratios [ORs] 2.12, 2.25, and 5.12, respectively; p < 0.05), whereas drainage significantly reduced this risk (OR, 0.28; p < 0.0001). Twelve patients (2.3% of the whole cohort and 16.4% of the deceased patients) presented with extremely rapid progression leading to fatal outcome, consistent with "fulminant AB." CONCLUSIONS: This study identified acute circulatory dysfunction and performance of drainage as independent predictive factors for 30-day AB-related mortality and revealed the existence of a fulminant AB sub-phenotype. Our findings could serve as a practical guide to predict the clinical outcomes of AB.

Erratum: Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande [Phys. Rev. Lett. 130, 031802 (2023)].

This corrects the article DOI: 10.1103/PhysRevLett.130.031802.

Postruminal choline supply during negative nutrient balance alters components of hepatic mTOR signaling and plasma amino acids in lactating Holstein cows.

Choline requirements for dairy cattle are unknown. However, enhanced postruminal supply of choline may increase flux through the methionine cycle to spare Met for other functions such as protein synthesis and phosphatidylcholine (PC) synthesis during periods of negative nutrient balance (NNB). The objective was to investigate the effects of postruminal choline supply during a feed restriction-induced NNB on hepatic abundance and phosphorylation of mTOR (mechanistic target of rapamycin)-related signaling proteins, hepatic lipidome and plasma AA. Ten primiparous rumen-cannulated Holstein cows (158 ± 24 DIM) were used in a replicated 5 × 5 Latin square design with 4 d of treatment and 10 d of recovery (14 d/period). Treatments were unrestricted intake with abomasal infusion of water, restricted intake (R; 60% of net energy for lactation requirements to induce NNB) with abomasal infusion of water (R0) or restriction plus abomasal infusion of 6.25, 12.5, or 25 g/d choline ion. Liver tissue was collected via biopsy on d 5 after infusions ended and used for Western blot analysis to measure proteins involved in mTOR signaling and untargeted lipidomics. Blood was collected on d 1 to 5 for plasma AA analysis. Statistical contrasts for protein and AA data were A0 versus R0 (CONT1), R0 versus the average of choline dose (CONT2) and tests of linear and quadratic effects of choline dose. Analysis of lipidomic data were performed with the web-based metabolomic processing tool MetaboAnalyst 5.0. Ratios of p-RPS6KB1:tRPS6KB1, p-EEF2:tEEF2, and p-EIF2:tEIF2 were greater with R (CONT1). Among those, supply of choline led to decreases in p-EEF2:tEEF2 (CONT2), p-EIF2:tEIF2 and tended to decrease p-EIF4BP1:tEIF4BP1. However, the effect was quadratic only for p-EEF2:tEEF2 and p-EIF2A:tEIF2A, reaching a nadir at 6.25 to 12.5 g/d choline ion. The ratio of p-RPS6KB1:tRPS6KB1 was not affected by supply of choline and was close to 2-fold greater at 25 g/d choline versus A0. Plasma Met concentration decreased with R (CONT1), but increased linearly with choline. Restriction also increased plasma 3-methyl-histidine (CONT1). The partial least squares discriminant analysis model of liver lipids distinguished treatments, with 13.4% of lipids being modified by treatment. One-way ANOVA identified 109 lipids with a false discovery rate ≤0.05. The largest group identified was PC species; all 35 detected decreased with R versus A0, but there were few differences among choline treatments. Overall, data suggested that dephosphorylation of EEF2 and EIF2A due to enhanced choline supply potentially helped maintain or increase protein synthesis during NNB. While activation of mTOR was not altered by choline, this idea of increased protein synthesis is partly supported by the increased circulating Met. However, enhanced postruminal choline had limited effects on the species of lipid produced during a period of NNB.

Search for Cosmic-Ray Boosted Sub-GeV Dark Matter Using Recoil Protons at Super-Kamiokande.

We report a search for cosmic-ray boosted dark matter with protons using the 0.37 megaton×years data collected at Super-Kamiokande experiment during the 1996-2018 period (SKI-IV phase). We searched for an excess of proton recoils above the atmospheric neutrino background from the vicinity of the Galactic Center. No such excess is observed, and limits are calculated for two reference models of dark matter with either a constant interaction cross section or through a scalar mediator. This is the first experimental search for boosted dark matter with hadrons using directional information. The results present the most stringent limits on cosmic-ray boosted dark matter and exclude the dark matter-nucleon elastic scattering cross section between 10^{-33}cm^{2} and 10^{-27}cm^{2} for dark matter mass from 1 MeV/c^{2} to 300 MeV/c^{2}.

Relationship of Lesion Location to Postoperative Steroid Use in Eosinophilic Chronic Rhinosinusitis.

OBJECTIVES: Eosinophilic chronic rhinosinusitis (ECRS) is known to recur after surgery. The treatment choice for recurrent ECRS, such as oral steroids or biological agents, must be chosen carefully, and identifying the lesion location may be useful. This study aimed to evaluate the postoperative course of ECRS patients and assess the relationship between endoscopic lesion location and postoperative oral steroid use. METHODS: Patients with chronic rhinosinusitis who underwent bilateral endoscopic sinus surgery from April 2018 to March 2020 were divided into two groups based on the presence or absence of oral steroid use after surgery. The primary endpoint was the lesion location on endoscopic findings during surgery: middle turbinate, middle meatus, superior turbinate, superior meatus, nasal septum, and sphenoethmoidal recess. Subjective symptoms, blood tests, and computerized tomography (CT) findings (Lund-Mackay score) were evaluated as secondary endpoints. RESULTS: Among 264 patients, 88 were diagnosed histologically with ECRS (mean 48.98 ± 1.40 years, 67 males/21 females). Twenty-three patients were steroid-using, 65 were steroid-free, and six stopped attending their appointments. Patients with sphenoethmoidal recess lesions were significantly more likely to require steroids (p = 0.019). There was a significant association between steroid use and younger age (p = 0.041), olfactory dysfunction (p = 0.021), and all sinuses (Frontal sinus: p < 0.001, Anterior ethmoid sinus: p = 0.002, Posterior ethmoid sinus: p = 0.011, Maxillary sinus: p = 0.018, Sphenoid sinus: p = 0.034, Total score: p < 0.001). CONCLUSION: A sphenoethmoidal recess lesion was a risk factor for requiring postoperative steroids. Young age, olfactory dysfunction, and preoperative severe CT findings were also significant risk factors. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2511-2516, 2023.

Increased plasma drug concentration and decreased additional insulin secretion following oral administration of glimepiride in Spontaneously Diabetic Torii rats.

We aimed to evaluate the pharmacokinetics and pharmacological effects of glimepiride in the Spontaneously Diabetic Torii (SDT) rat, which is a non-obese model of type 2 diabetes. After oral administration of glimepiride (10 mg/kg), the maximum plasma concentrations and the area under the curve from 0 to 6 h of glimepiride in SDT rats were significantly higher than those in age-matched Sprague-Dawley rats. Whereas, additional insulin secretion following glimepiride treatment was markedly reduced in SDT rats. Thus, the SDT rat can be regarded as a model that reflects type 2 diabetes with reduced insulin secretory capacity. Our findings suggested that glimepiride could be ineffective in sever type 2 diabetic patients.

Lactational performance and plasma and muscle amino acid concentrations in dairy cows fed diets supplying 2 levels of digestible histidine and metabolizable protein.

The objective of this experiment was to investigate the effect of dietary levels of digestible histidine (dHis) and MP on lactational performance and plasma and muscle concentrations of free AA in dairy cows. A randomized block design experiment was conducted with 48 Holstein cows, including 20 primiparous, averaging (±SD) 103 ± 22 d in milk and 45 ± 9 kg/d milk yield at the beginning of the experiment. A 2-wk covariate period preceded 12 experimental wk, of which 10 wk were for data and sample collection. Experimental treatments were (1) MP-adequate (MPA) diet with 2.1% dHis of MP (MPA2.1), (2) MPA with 3.0% dHis (MPA3.0), (3) MP-deficient (MPD) diet with 2.1% dHis (MPD2.1), and (4) MPD with 3.0% dHis (MPD3.0). Actual dHis supply was estimated at 64, 97, 57, and 88 g/d, respectively. Diets supplied MP at 110% (MPA) and 96% (MPD) of NRC 2001 dairy model requirements calculated based on DMI and production data during the experiment. Dry matter intake and milk yield data were collected daily, milk samples for composition and blood samples for AA analysis were collected every other week, and muscle biopsies at the end of covariate period, and during wk 12 of the experiment. The overall DMI was not affected by dHis or MP level. Milk yield tended to be increased by 3.0% dHis compared with 2.1% dHis. Milk true protein concentration and yield were not affected by treatments, whereas milk urea nitrogen concentration was lower for MPD versus the MPA diet. Milk fat concentration was lower for MPD versus MPA. There was a MP × dHis interaction for milk fat yield and energy-corrected milk; milk fat was lower for MPD3.0 versus MPD2.1, but similar for cows fed the MPA diet regardless of dHis level whereas energy-corrected milk was greater for MPA3.0 versus MPA2.1 but tended to be lower for MPD3.0 versus MPD2.1. Plasma His concentration was greater for cows fed dHis3.0, and concentration of sum of essential AA was greater, whereas carnosine, 1-Methyl-His and 3-Methyl-His concentrations were lower for cows fed MPA versus MPD diet. Muscle concentration of His was greater for cows fed dHis3.0 treatment. The apparent efficiency of His utilization was increased at lower MP and His levels. Overall, cows fed a corn silage-based diet supplying MP at 110% of NRC (2001) requirements tended to have increased ECM yield and similar milk protein yield to cows fed a diet supplying MP at 96% of requirements. Supplying dHis at 3.0% of MP (or 86 and 96 g/d, for MPD3.0 and MPA3.0, respectively) tended to increase milk yield and increased plasma and muscle concentrations of His but had minor or no effects on other production variables in dairy cows.

Chemotactic responses of Brugia pahangi infective third-stage larvae to tris(hydroxymethyl)aminomethane-related compounds and amino acids.

Since the exogenous compound tris(hydroxymethyl)aminomethane (Tris) showed a potent chemoattractant activity for Brugia pahangi infective third-stage larvae (L3), it was assumed that, in natural infection to a host, filarial L3 can be expected to recognize an endogenous Tris-related compound. In addition, a few amino acids have been identified as water-soluble attractants for second-stage juveniles of Meloidogyne incognita, a plant parasitic nematode. Therefore, the present study assesses the in vitro chemotactic responses of B. pahangi L3 to Tris-related compounds and amino acids using an agar-plate assay. Among Tris-related compounds, 2-amino-1,3-propanediol (APD) and 2-amino-2-methyl-1,3-propanediol (AMPD) exhibited a potent chemoattractant activity for filarial L3 at a level similar to Tris. Furthermore, arginine (Arg) was identified as a potent attractant for filarial L3 among amino acids. In addition, filarial L3 were attracted to Arg, APD and AMPD in mild alkaline conditions rather than acidic conditions. The chemoattractant activity of the three compounds for filarial L3 was observed in concentrations between 6.3 and 200 mm. This is the first report to demonstrate that Arg, APD and AMPD are potent chemoattractants for B. pahangi L3. Endogenous Arg and APD, in particular, may be involved in the regulation of the chemotactic behaviour of filarial L3 in the infection to a host. The present results will help to elucidate the mechanism of filarial skin-penetrating invasion of a host.

Dietary starch level and rumen-protected methionine, lysine, and histidine: Effects on milk yield, nitrogen, and energy utilization in dairy cows fed diets low in metabolizable protein.

Our objective was to investigate the interactions between starch level and rumen-protected Met, Lys, His (RP-MLH) on milk yield, plasma AA concentration, and nutrient utilization in dairy cows fed low metabolizable protein diets (mean = -119 g/d of metabolizable protein balance). Sixteen multiparous Holstein cows (138 ± 46 d in milk, 46 ± 6 kg/d in milk) were used in a replicated 4 × 4 Latin square with a 2 × 2 factorial arrangement of treatments. Each period lasted 21 d with 14 d for diet adaptation and 7 d for data and sample collection. Dietary starch level varied by replacing (dry matter basis) pelleted beet pulp and soyhulls with ground corn resulting in the following treatments: (1) 20% pelleted beet pulp and 10% soyhulls (reduced starch = RS), (2) RS plus RP-MLH (RS+AA), (3) 30% ground corn (high starch = HS), and (4) HS plus RP-MLH (HS+AA). Dietary starch concentrations averaged 12.3 and 34.4% for RS and HS basal diets, respectively. Diets were supplemented with RP-MLH products to supply digestible Met, Lys, and His. Compared with RS and RS+AA diets, HS and HS+AA diets increased yields of milk (37.9 vs. 40.1 kg/d) and milk protein (1.07 vs. 1.16 kg/d) and decreased dry matter intake (25.9 vs. 25.2 kg/d), milk urea N (12.6 vs. 11.0 mg/dL), and plasma urea N (13.3 vs. 11.6 mg/dL). Milk N efficiency was greater in cows fed the HS and HS+AA than RS and RS+AA diets (28.9 vs. 25%), and RP-MLH supplementation improved milk true protein concentration. Starch level × RP-MLH interactions were observed for plasma concentrations of Arg and Lys, with RP-MLH being more effective to increase plasma Arg (+16%) and Lys (+23%) when supplemented to the RS than the HS basal diet. Replacing pelleted beet pulp and soyhulls with ground corn lowered the plasma concentrations of all essential AA except Met and Thr. In addition, the plasma concentrations of His and Met increased with RP-MLH. The apparent total-tract digestibilities of neutral and acid detergent fiber were lower, and those of starch and ether extract greater in cows offered the HS and HS+AA diets than RS and RS+AA diets. Urinary excretion of urea N decreased by replacing pelleted beet pulp and soyhulls with ground corn. Enteric CH4 production, CH4 yield, and CH4 intensity all decreased in the HS and HS+AA versus RS and RS+AA diets. Diets did not affect the intakes of gross energy, metabolizable energy, and net energy of lactation. In contrast, digestible energy intake increased with feeding the RS and RS+AA diets, whereas CH4 energy decreased in cows fed the HS and HS+AA diets. Supplementation with RP-MLH had no effect on energy utilization variables. Overall, the lack of interactions between dietary starch level and RP-MLH supplementation on most variables measured herein showed that the effects of starch intake and RP-MLH were independent or additive.

Histidine dose-response effects on lactational performance and plasma amino acid concentrations in lactating dairy cows: 1. Metabolizable protein-adequate diet.

The objective of this experiment was to determine the effect of increasing digestible His (dHis) doses on milk production, milk composition, and plasma AA concentrations in lactating dairy cows fed diets that meet or exceed their energy and metabolizable protein (MP) requirements. In a companion paper (Räisänen et al., 2021) results are presented on the effect of increasing dHis dose with an MP-deficient basal diet. In this experiment, 16 Holstein cows (72 ± 15 d in milk) were used in a replicated 4 × 4 Latin square design experiment with four 28-d periods. Treatments were as follows: (1) control, total mixed ration (TMR) with 1.8% dHis of MP (TMR1; dHis1.8); (2) a different TMR with 2.2% dHis (TMR2; dHis2.2); (3) TMR2 supplemented with rumen-protected His (RP-His) to supply 2.6% dHis (dHis2.6); and (4) TMR2 supplemented with RP-His to supply 3.0% dHis of MP (dHis3.0). Estimated dHis intakes calculated at the end of the experiment were 46, 58, 69, and 79 g/d for dHis1.8, dHis2.2, dHis2.6, and dHis3.0, respectively. Contrasts were used to compare TMR1 with TMR2 and to test the linear and quadratic effects of RP-His inclusion rate on TMR2. We detected no effects of TMR or dHis dose on dry matter intake or milk yield, whereas energy-corrected milk (ECM) yield was quadratically increased, being greatest for cows on treatment dHis2.6. Milk true protein and lactose concentrations and milk true protein yield were not affected by TMR or dHis dose. Milk fat concentration and yield increased quadratically, and lactose yield tended to increase quadratically with increasing dHis dose. Calculated apparent efficiency of His utilization decreased quadratically with increasing dHis supply. Further, plasma concentration of His was greater for cows on TMR2 compared with TMR1. When an MP-adequate diet was fed to dairy cows, milk true protein concentration and yield were not affected by dHis supply, but milk fat and ECM yields of dairy cows were optimized at dHis supply of 69 g/d or 2.65% of MP.

Histidine dose-response effects on lactational performance and plasma amino acid concentrations in lactating dairy cows: 2. Metabolizable protein-deficient diet.

The objective of this experiment was to determine the effect of increasing digestible His (dHis) levels with a rumen-protected (RP) His product on milk production, milk composition, and plasma AA concentrations in lactating dairy cows fed a metabolizable protein (MP)-deficient diet, according to the National Research Council dairy model from 2001. The companion paper presents results on the effect of increasing dHis dose with a MP-adequate basal diet. Twenty Holstein cows, of which 8 were rumen-cannulated, were used in a replicated 4 × 4 Latin square design experiment with four 28-d periods. Treatments were a control diet supplying 1.8% dHis of MP or 37 g/d (dHis1.8) and the control diet supplemented RP-His to provide 2.2, 2.6, or 3.0%, dHis of MP, or 53, 63, and 74 g/d (dHis2.2, dHis2.6, and dHis3.0, respectively). Histidine dose did not affect dry matter intake, but milk yield increased quadratically and energy-corrected milk yield increased linearly with increasing dHis dose. Histidine dose had a quadratic effect on milk fat concentration but did not affect milk fat yield. Lactose concentration decreased linearly, whereas lactose yield increased linearly with increasing dHis dose. There was a tendency for a linear increase in milk true protein concentration, and milk true protein yield increased linearly with dHis dose. Further, plasma His concentration increased linearly with increasing dHis dose and calculated apparent efficiency of His utilization decreased quadratically with increasing dHis supply. Histidine had minor or no effects on rumen fermentation. In the conditions of this experiment, RP-His supplementation of an MP-deficient corn silage-based diet increased milk yield linearly up to a dHis supply of 63 g/d (or 2.6% dHis of MP) and increased feed efficiency, energy-corrected milk yield and milk true protein yield linearly up to a dHis supply of 74 g/d (or 3.0% dHis of MP) in lactating dairy cows.

Choline supply during negative nutrient balance alters hepatic cystathionine ß-synthase, intermediates of the methionine cycle and transsulfuration pathway, and liver function in Holstein cows.

Although choline requirements for cows are unknown, enhanced postruminal supply may decrease liver triacylglycerol and increase flux through the Met cycle to improve immunometabolic status during a negative nutrient balance (NNB). Our objectives were to investigate the effects of postruminal choline supply during a feed restriction-induced NNB on (1) hepatic activity cystathionine ß-synthase and transcription of enzymes in the transsulfuration pathway and Met cycle; (2) hepatic metabolites in the Met cycle and the transsulfuration pathway, bile acids, and energy metabolism; and 3) plasma biomarkers of liver function, inflammation, and oxidative stress. Ten primiparous rumen-cannulated Holstein cows (158 ± 24 d postpartum) were used in a replicated 5 × 5 Latin square design with 4-d treatment periods and 10 d of recovery (14 d/period). Treatments were unrestricted intake with abomasal infusion of water, restricted intake (R; 60% of net energy for lactation requirements) with abomasal infusion of water, or R plus abomasal infusion of 6.25, 12.5, or 25 g/d choline ion. Liver tissue was collected on d 5 after infusions ended, and blood was collected on d 1, 3, and 5. Statistical contrasts were A0 versus R0 (CONT1), R versus the average of choline doses (CONT2), and tests of linear and quadratic effects of choline dose. Activity of cystathionine ß-synthase was lower with R (CONT1) and decreased linearly with choline. Hepatic glutathione was not different with R or choline, but taurine tended to be greater with choline (CONT2). Betaine and carnitine were greater with R (CONT1) and further increased with choline (CONT2). Concentrations of NAD+ were greater with choline (CONT2). Cholic and glycol-chenodeoxycholic acids were decreased by R and choline, while taurocholic and tauro-chenodeoxycholic acids were not altered. Plasma aspartate aminotransferase and bilirubin were greater with R (CONT1) but decreased with choline (CONT2). Paraoxonase was lower with R and increased with choline (CONT2). Data suggest that enhanced supply of choline during NNB decreases entry of homocysteine to the transsulfuration pathway, potentially favoring remethylation to Met by acquiring a methyl group from betaine. As such, Met may provide methyl groups for synthesis of carnitine. Along with production data indicating that 12.5 g/d choline ion improved milk yield and liver fatty acid metabolism during NNB, the changes in blood biomarkers also suggest a beneficial effect of choline supply on liver function and oxidative stress.

Incremental amounts of rumen-protected histidine increase plasma and muscle histidine concentrations and milk protein yield in dairy cows fed a metabolizable protein-deficient diet.

The dairy industry can benefit from low crude protein (CP) diets due to reduced N excretion, but shortages of Met, Lys, and His may limit milk protein synthesis. We studied the effect of incremental amounts of rumen-protected (RP)-His on plasma and muscle AA profile, nutrient utilization, and yields of milk and milk true protein in dairy cows. Eight multiparous Holstein cows (130 ± 30 d in milk) were randomly assigned to treatment sequences in a replicated 4 × 4 Latin square design with 28-d experimental periods. Treatments included a basal diet composed (dry matter basis) of 50% corn silage, 15% haylage, and 35% concentrate supplemented with 0, 82, 164, and 246 g/d of RP-His and 11 g/d of RP-Met. Milk, plasma, and muscle samples were collected weekly or every other week during all 4 periods, whereas spot urine and fecal grab samples were taken only in wk 4 of each period. Data were analyzed individually by week using linear, quadratic, and cubic orthogonal polynomials and repeated measures. Plasma His increased linearly with RP-His during wk 1 (30.3 to 57.2 µM) to wk 4 (33.2 to 63.1 µM). Plasma carnosine increased linearly with supplemental RP-His except in wk 2. No treatment effect was observed for plasma 3-methylhistidine except a quadratic effect in wk 3. Inclusion of RP-His showed linear effects on muscle His in wk 2 (20.1 to 32.5 µM) and 4 (20.3 to 35.5 µM). Whereas muscle anserine and carnosine concentrations were not affected by treatments in wk 4, anserine responded quadratically and carnosine showed a trend for a quadratic response to RP-His in wk 2. During wk 4, treatments did not affect urinary excretion of total purine derivatives, as well as dry matter intake and milk concentrations of fat and true protein. In contrast, milk yield tended to increase linearly (31.2 to 32.7 kg/d) and milk true protein yield responded linearly (0.93 to 0.98 kg/d) and tended to increase quadratically to RP-His supplementation in wk 4. Also, milk urea-N (11.7 to 12.9 mg/dL) and urinary excretion of urea-N (23.7 to 27.0% of N intake) increased linearly with feeding RP-His in wk 4. Overall, RP-His was effective to enhance plasma and muscle concentrations of His and milk protein synthesis. Elevated milk urea-N and urinary excretion of urea-N suggest that plasma His may have exceeded the requirement with excess N converted to urea in the liver. Future research is needed to determine the bioavailability of RP-His supplements to improve the accuracy of diet formulation for AA.

Optimal Settings for Double Filtration Plasmapheresis With Targeted Removal Rate of Preexisting Antibody in Antibody-Incompatible Kidney Transplant.

BACKGROUND: Elimination of preexisting donor-reactive antibodies is essential for antibody-incompatible kidney transplantation. Double filtration plasmapheresis (DFPP) using albumin (Alb) replacement fluid (Rf) removes immunoglobulin more selectively than plasma exchange; however, fixed-dose treatment can result in insufficient removal of antibody or excess loss of osmotic pressure and subsequent hypotension. The aim of this study was to determine the optimal setting (volume and concentration of Rf) of DFPP to remove donor-reactive antibodies. MATERIALS AND METHODS: One hundred seventeen DFPPs were performed in 41 patients for kidney transplant in an ABO-incompatible or crossmatch-positive setting. A formula for Rf volume was determined based on volume-removal rate (RR) curve of IgG. Another formula for Alb concentration of Rf was also established to keep plasma volume within pre-DFPP plasma volume ± 10% calculated by post- to pre-DFPP hematocrit ratio to avoid hypotensive events. RESULTS: RR-IgG was obtained based on patient data: Rf (mL) = BW (kg) × eX, [X = (RR-IgG + 10.757)/25.603] (R2 = 0.401, P < .001). Rf Alb concentration was determined by AlbRf ≥ (2.982 - 2.36 × RR-IgG) × Albpre + (2.36 × RR-IgG - 0.236) × pre-DFPP total protein. CONCLUSIONS: Optimal volume and concentration of Alb Rf can be calculated using our formulae with targeted RR-IgG.

Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande.

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.

Comparison of electrochemiluminescence immunoassay and latex agglutination turbidimetric immunoassay for evaluation of everolimus blood concentrations in renal transplant patients.

WHAT IS KNOWN AND OBJECTIVE: For analysis of blood concentrations of everolimus, many hospital laboratories use either latex agglutination turbidimetric immunoassay (LTIA) or electrochemiluminescence immunoassay (ECLIA). However, no studies have compared both immunoassay methods under the same conditions. Accordingly, in this study, we compared everolimus blood concentrations obtained by LTIA and ECLIA in renal transplant patients. METHODS: Blood samples (n = 230) from 60 renal transplant patients (19 female and 41 male) were evaluated using both immunoassays. Subsequently, we switched the assay for detection of everolimus blood concentrations from LTIA to ECLIA as a clinical application. Three quality control (QC) samples for LTIA were analysed using ECLIA, and 3 QC samples for ECLIA were analysed using LTIA. RESULTS: The Deming regression of ECLIA versus LTIA generated the following parameters: slope, 1.0067 and intercept, 1.7489 ng/mL, in the analysis of 230 samples. Bland-Altman analysis showed an average positive bias of 1.73 ng/mL between ECLIA and LTIA. When the clinical apparatus was switched from LTIA to ECLIA, the average everolimus blood concentration assayed by LTIA before switching was 3.57 ng/mL, whereas that by ECLIA after switching in the same patients taking the same daily dose (mean: 1.43 mg/day) was 5.85 ng/mL. The QCs assayed using LTIA were lower by an average of 67.3% (range: 55.8%-79.5%) for ECLIA, and in the same 230 samples from patients, the everolimus blood concentrations assayed by LTIA were lower by an average of 67.4% (range: 37.1%-114.5%) of ECLIA. WHAT IS NEW AND CONCLUSION: Analysis of everolimus concentrations by immunoassays with high precision and accuracy is required to ensure long-term survival of transplant recipients. Although the concentrations of QCs and calibrators of everolimus in LTIA were previously corrected to 70% concentration because of cross-reactivity with everolimus metabolites, these adjustments may need to be reviewed.

Risk of new-onset diabetes mellitus during treatment with low-dose statins in Japan: A retrospective cohort study.

WHAT IS KNOWN AND OBJECTIVE: The risk of new-onset diabetes mellitus (NODM) in Japanese patients using low-dose hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) has not been previously examined. The aim of this study was to assess the risk of NODM associated with use of high- and low-potency statins in Japanese patients taking low-dose statins. METHODS: A retrospective cohort study of 2554 Japanese patients who started treatment with a statin was conducted. Only patients taking the same dose of the same statin were enrolled, and patients were separated into high- and low-potency statin groups. The outcome was incidence of NODM during statin treatment. RESULTS: The incidence rate of NODM in the cohort was 7.4% (n = 190). Kaplan-Meier survival curves showed a significantly higher rate of NODM in patients taking high-potency statins compared with those taking low-potency statins (P < .001, log-rank test). Baseline fasting plasma glucose levels, use of high-potency statins, male gender and combination treatment with calcium channel blockers, immunosuppressants or steroids were identified as factors that significantly increased the risk for NODM using Cox proportional hazard regression analysis. WHAT IS NEW AND CONCLUSION: The use of high-potency statins at a low standard daily dose significantly increased the risk of NODM in Japanese patients compared with low-potency statins. Furthermore, clinicians should also be careful when prescribing statins in combination with steroids or immunosuppressants due to the increased risk of NODM.