Summary
Background
The number of reported cases of allergic reactions to sesame seeds (Sesamum indicum) has increased significantly. The specific IgE tests and skin prick tests presently available ...for diagnosis of sesame allergy are all based on crude sesame extract and are limited by their low clinical specificity. Thus, oral food challenge (OFC) is still the gold standard in the diagnosis.
Objective
The aim was to identify the allergen components useful to diagnose sesame‐allergic children with the goal to reduce the number of OFCs needed.
Methods
Ninety‐two sesame‐sensitized children were consecutively enrolled and diagnosed based on OFC or convincing history. Specific IgE to purified native 11S globulin (nSes i 11S), 7S globulin (nSes i 7S), 2S albumin (nSes i 2S), and two recombinant 2S albumins (rSes i 1 and rSes i 2) was measured by ELISA and/or ImmunoCAP (rSes i 1/streptavidin application).
Results
Based on area under curve (AUC) values from receiver operating characteristic (ROC) analysis, rSes i 1 was shown to have the best diagnostic performance of the allergen components in ELISA. The experimental rSes i 1 ImmunoCAP test had larger AUC (0.891; 95% CI, 0.826–0.955) compared to the commercially available sesame ImmunoCAP (0.697; 95% CI, 0.589–0.805). The clinical sensitivity and specificity for the rSes i 1 ImmunoCAP test at optimal cut‐off (3.96 kUA/L) were 86.1% and 85.7%, respectively.
Conclusion and Clinical Relevance
Sensitization to Ses i 1 is strongly associated with clinical sesame allergy. Measurement of specific IgE to rSes i 1 could reduce the numbers of OFCs needed.
Clinicians, including anesthesiologists, surgeons, and intensivists, are frequently called on to correct coagulopathy in patients receiving oral anticoagulation therapy. Before elective surgery, ...anticoagulation reversal may be undertaken over several days by discontinuing warfarin or vitamin K treatment, but rapid correction is required in an emergency. European and American guidelines recommend prothrombin complex concentrates (PCCs) for anticoagulation reversal in patients with life-threatening bleeding and an increased international normalized ratio. Compared with human fresh frozen plasma, PCCs provide quicker correction of the international normalized ratio and improved bleeding control. Although there are historic concerns regarding potential infectious and thrombotic risks with PCCs, current PCC formulations are much improved. Recombinant activated factor VII is a potential alternative to PCCs, but preclinical comparisons suggest that PCCs are more effective in correcting coagulopathy. Although many patients who require rapid reversal of warfarin are currently treated with fresh frozen plasma, PCCs should be considered as an alternative therapy.
Background
Sensitization to the carbohydrate galactose‐α‐1,3‐galactose (α‐Gal) has been reported in patients with beef allergy. However, the proteins responsible for this allergy have not yet been ...identified. This study aimed to identify beef proteins that predominantly react with serum IgE in Japanese patients with beef allergy.
Methods
Sera were collected from 29 patients with beef allergy who had allergic reaction(s) such as urticaria, abdominal pain, vomiting, and anaphylactic shock after ingestion of beef and pork; the sera tested positive for IgE against beef and pork. IgE‐binding proteins were detected by immunoblotting sera from the patients and identified using a combination of two‐dimensional gel electrophoresis and peptide mass fingerprinting techniques. The involvement of carbohydrate in the binding of IgE to allergens was examined by periodate treatment and an inhibition assay with cetuximab by immunoblotting. Specific IgE binding to cetuximab was measured using the CAP‐fluorescent enzyme immunoassay.
Results
Two IgE‐binding proteins (240 kDa and 140 kDa) were detected in beef extract and identified as laminin γ‐1 and the collagen α‐1 (VI) chain from Bos taurus, respectively. Periodate treatment or the inhibition assay resulted in the loss of IgE binding to these proteins. Immunoblotting with anti‐α‐Gal antibody revealed the presence of α‐Gal on the 240‐ and 140‐kDa beef proteins. The amount of IgE bound to cetuximab was significantly correlated with that to beef in the patients with beef allergy.
Conclusion
The carbohydrate moiety (α‐Gal) on laminin γ‐1 and collagen α‐1 (VI) chain are possibly common IgE‐reactive proteins in the Japanese patients with beef allergy.
We study an array of ultracold atoms in an optical lattice (Mott insulator) excited with a coherent ultrashort laser pulse to a state where single-electron wave functions spatially overlap. Beyond a ...threshold principal quantum number where Rydberg orbitals of neighboring lattice sites overlap with each other, the atoms efficiently undergo spontaneous Penning ionization resulting in a drastic change of ion-counting statistics, sharp increase of avalanche ionization, and the formation of an ultracold plasma. These observations signal the actual creation of electronic states with overlapping wave functions, which is further confirmed by a significant difference in ionization dynamics between a Bose-Einstein condensate and a Mott insulator. This system is a promising platform for simulating electronic many-body phenomena dominated by Coulomb interactions in the condensed phase.
Summary
Hepatocellular carcinoma (HCC) is a serious complication of hepatitis C virus (HCV) infection. Sustained virologic response (SVR) for HCV is associated with a reduction in cirrhosis, HCC and ...mortality and their associated costs. Japanese HCV patients are older with higher prevalence of HCC. Here we used a decision‐analytic Markov model to estimate the economic benefit of HCV cure by reducing HCC and DCC burden in Japan. A cohort of 10 000 HCV genotype 1b (GT1b) Japanese patients was modelled with a hybrid decision tree and Markov state‐transition model capturing natural history of HCV over a lifetime horizon. Treatment options were approved all‐oral direct‐acting anti‐virals (DAAs) vs no treatment. Treatment efficacy was based on clinical trials and transition rates and costs obtained from Japan‐specific data. Cases of HCC, decompensated cirrhosis (DCC) and quality‐adjusted life years (QALYs) were projected for patients treated with DAAs vs NT. QALYs were monetized using a willingness‐to‐pay threshold of ¥4‐to‐¥6 million. Incremental savings with treatment were calculated by adding the projected cost of complications avoided to the monetized gains in QALYs. The model showed that DAA treatment vs no treatment, reduces 2057 cases of HCC and 1478 cases of decompensated cirrhosis and saves ¥850 446.73 and ¥338 229.90 per patient (ppt). Additionally, treatment can lead to additional 2.64 QALYs gained per patient. The indirect economic gains associated with treatment‐related QALY improvements were ¥10 576 000, ¥13 220 000 and ¥15 864 000 ppt (willingness‐to‐pay thresholds of ¥4 million, ¥5 million and ¥6 million). Total economic savings of treatment with DAAs (vs no treatment) was ¥7 526 372.63, ¥10 170 372.63 and ¥12 814 372.63, at these different willingness‐to‐pay thresholds. In conclusion treatment of HCV GT1b with all‐oral DAAs in Japan can lead to significant direct and indirect savings related to avoidance of HCC and DCC.
BACKGROUND
Perioperative use of allogeneic blood products is associated with higher morbidity, mortality, and hospital costs after cardiac surgery. Blood conservation techniques such as acute ...normovolemic hemodilution (ANH) report variable success. We hypothesized that large‐volume ANH with limited hemodilution would reduce allogeneic blood transfusion compared to the standard practice.
STUDY DESIGN AND METHODS
Retrospective observational study of cardiac surgery patients at the University of Maryland Medical Center between January 2014 and September 2017. Using the institutional Society of Thoracic Surgeons database 91 autologous and 981 control patients who underwent coronary artery bypass grafting, aortic valve replacement, or both were identified. After propensity matching of 13 preoperative characteristics, 84 autologous and 84 control patients were evaluated. Our primary endpoint was avoidance of blood transfusion during index hospitalization, and secondary endpoints were postoperative bleeding and major adverse outcomes.
RESULTS
The median harvest volumes in the ANH and control groups were 1100 mL and 400 mL, respectively. Of the ANH group, 25% received any transfusion versus 45.2% of the control group after propensity score matching (p < 0.006). When controlling for preoperative platelet count, the transfusion rate ratios for ANH were 0.58 (95% confidence interval, 0.39–0.88) for RBCs and 0.63 (0.44–0.89) for non‐RBC components, which were both found to be statistically significant. There was no difference found in major adverse events.
CONCLUSION
These results suggest that large‐volume ANH is beneficial in reducing both RBC and non‐RBC component usage in cardiac surgery. A further prospective validation is warranted.
In this phase Ib study, four combination therapies of nivolumab 10 mg/kg and standard chemotherapy (cisplatin/gemcitabine, cisplatin/pemetrexed, carboplatin/paclitaxel/bevacizumab, or docetaxel) ...showed acceptable toxicity profiles in patients with advanced non-small-cell lung cancer. Furthermore, these combination therapies presented encouraging antitumor activities.
The human IgG4 monoclonal antibody nivolumab targets programmed cell death-1 (PD-1) and promotes antitumor response by blocking the interaction of PD-1 with its ligands. This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC).
Patients who had stage IIIB without indication for definitive radiotherapy, stage IV, or recurrent NSCLC were eligible. Regimens were nivolumab 10 mg/kg + gemcitabine/cisplatin (arm A), pemetrexed/cisplatin (arm B), paclitaxel/carboplatin/bevacizumab (arm C), or docetaxel (arm D). Regimens A, B, and D were repeated every 3 weeks for up to four cycles and regimen C was repeated for up to six cycles; nivolumab alone (arm A), with pemetrexed (arm B), bevacizumab (arm C), or docetaxel (arm D) was continued every 3 weeks as maintenance therapy until disease progression or unacceptable toxicity. Dose-limiting toxicity (DLT) was evaluated during the first treatment cycle.
As of March 2014, six patients were enrolled in each arm. The combination of nivolumab 10 mg/kg and chemotherapy was well tolerated. DLT was observed in only one patient in arm A (alanine aminotransferase increased). Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively. Three, three, six, and one patient achieved partial response while median progression-free survival was 6.28, 9.63 months, not reached, and 3.15 months in arms A, B, C, and D, respectively.
Combination of nivolumab 10 mg/kg and chemotherapy showed an acceptable toxicity profile and encouraging antitumor activity in patients with advanced NSCLC.
Japanese Pharmaceutical Information Center Clinical Trials Information (JapicCTI)-132071.
High flexural strength of computer-aided manufacturing resin composite blocks (CAD/CAM RCBs) are required in clinical scenarios. However, the conventional in vitro approach of modifying materials’ ...composition by trial and error was not efficient to explore the effective components that contribute to the flexural strength. Machine learning (ML) is a powerful tool to achieve the above goals. Therefore, the aim of this study was to develop ML models to predict the flexural strength of CAD/CAM RCBs and explore the components that affect flexural strength as the first step. The composition of 12 commercially available products and flexural strength were collected from the manufacturers and literature. The initial data consisted of 16 attributes and 12 samples. Considering that the input data for each sample were recognized as a multidimensional vector, a fluctuation range of 0.1 was proposed for each vector and the number of samples was augmented to 120. Regression algorithms—that is, random forest (RF), extra trees, gradient boosting decision tree, light gradient boosting machine, and extreme gradient boosting—were used to develop 5 ML models to predict flexural strength. An exhaustive search and feature importance analysis were conducted to analyze the effective components that affected flexural strength. The R2 values for each model were 0.947, 0.997, 0.998, 0.983, and 0.927, respectively. The relative errors of all the algorithms were within 15%. Among the high predicted flexural strength group in the exhaustive search, urethane dimethacrylate was contained in all compositions. Filler content and triethylene glycol dimethacrylate were the top 2 features predicted by all models in the feature importance analysis. ZrSiO4 was the third important feature for all models, except the RF model. The ML models established in this study successfully predicted the flexural strength of CAD/CAM RCBs and identified the effective components that affected flexural strength based on the available data set.
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