Tacrolimus Treatment for TAFRO Syndrome.

TAFRO syndrome is an acute systemic inflammatory disorder characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly. While its lymph node pathology is similar to that of idiopathic multicentric Castleman disease (iMCD), the clinical features of TAFRO syndrome differ from those of typical iMCD, as they include a more aggressive clinical course and high mortality. However, an optimal treatment strategy for TAFRO syndrome has not yet been established, owing to a poor understanding of its pathogenesis. The limited cases we encountered suggest that tacrolimus treatment in combination with glucocorticoids may potentially be effective and well tolerated as an initial treatment, and hold promise as a glucocorticoid-sparing agent. Herein, we report an additional case and review the sparse literature available regarding TAFRO syndrome treated via tacrolimus.

Elevated Leukocyte Count and Platelet-Derived Thrombogenicity Measured Using the Total Thrombus-Formation Analysis System in Patients with ST-Segment Elevation Myocardial Infarction.

AIMS: High platelet-derived thrombogenicity during the acute phase of ST-segment elevation myocardial infarction (STEMI) is associated with poor outcomes; however, the associated factors remain unclear. This study aimed to examine whether acute inflammatory response after STEMI affects platelet-derived thrombogenicity. METHODS: This retrospective observational single-center study included 150 patients with STEMI who were assessed for platelet-derived thrombogenicity during the acute phase. Platelet-derived thrombogenicity was assessed using the area under the flow-pressure curve for platelet chip (PL-AUC), which was measured using the total thrombus-formation analysis system (T-TAS). The peak leukocyte count was evaluated as an acute inflammatory response after STEMI. The patients were divided into two groups: the highest quartile of the peak leukocyte count and the other three quartiles combined. RESULTS: Patients with a high peak leukocyte count (＞15,222/mm3; n=37) had a higher PL-AUC upon admission (420 [386-457] vs. 385 [292-428], p=0.0018), higher PL-AUC during primary percutaneous coronary intervention (PPCI) (155 [76-229] vs. 96 [29-170], p=0.0065), a higher peak creatine kinase level (4200±2486 vs. 2373±1997, p＜0.0001), and higher PL-AUC 2 weeks after STEMI (119 [61-197] vs. 88 [46-122], p=0.048) than those with a low peak leukocyte count (≤ 15,222/mm3; n=113). The peak leukocyte count after STEMI positively correlated with PL-AUC during primary PPCI (r=0.37, p＜0.0001). A multivariable regression analysis showed the peak leukocyte count to be an independent factor for PL-AUC during PPCI (ß=0.26, p=0.0065). CONCLUSIONS: An elevated leukocyte count is associated with high T-TAS-based platelet-derived thrombogenicity during the acute phase of STEMI.

Platelet-Derived Thrombogenicity Measured by Total Thrombus-Formation Analysis System in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention.

BACKGROUND: Prompt and potent antiplatelet effects are important aspects of management of ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). We evaluated the association between platelet-derived thrombogenicity during PPCI and enzymatic infarct size in STEMI patients.Methods and Results:Platelet-derived thrombogenicity was assessed in 127 STEMI patients undergoing PPCI by: (1) the area under the flow-pressure curve for the PL-chip (PL18-AUC10) using the total thrombus-formation analysis system (T-TAS); and (2) P2Y12reaction units (PRU) using the VerifyNow system. Patients were divided into 2 groups (High and Low) based on median PL18-AUC10during PPCI. PRU levels during PPCI were suboptimal in both the High and Low PL18-AUC10groups (median [interquartile range] 266 [231-311] vs. 272 [217-317], respectively; P=0.95). The percentage of final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was lower in the High PL18-AUC10group (75% vs. 90%; P=0.021), whereas corrected TIMI frame count (31.3±2.5 vs. 21.0±2.6; P=0.005) and the incidence of slow-flow/no-reflow phenomenon (31% vs. 11%, P=0.0055) were higher. The area under the curve for creatine kinase (AUCCK) was greater in the High PL18-AUC10group (95,231±7,275 IU/L h vs. 62,239±7,333 IU/L h; P=0.0018). Multivariate regression analysis identified high PL18-AUC10during PPCI (ß=0.29, P=0.0006) and poor initial TIMI flow (ß=0.37, P<0.0001) as independent determinants of AUCCK. CONCLUSIONS: T-TAS-based high platelet-derived thrombogenicity during PPCI was associated with enzymatic infarct size in patients with STEMI.

Impact of Total Antithrombotic Effect on Bleeding Complications in Patients Receiving Multiple Antithrombotic Agents.

BACKGROUND: Few reports have evaluated the total antithrombotic effect of multiple antithrombotic agents. Methods and Results: Thrombus formation was evaluated with the Total Thrombus-formation Analysis System (T-TAS®) using 2 types of microchips in 145 patients with stable coronary artery disease receiving oral anticoagulants plus single- or dual-antiplatelet therapy. The PL-chip coated with collagen is designed for analysis of the platelet thrombus formation process under shear stress condition (18 µL/min). The AR-chip coated with collagen and tissue thromboplastin is designed for analysis of the fibrin-rich platelet thrombus formation process under shear stress condition (4 µL/min). The results were expressed as an area under the flow pressure curve (PL18-AUC10and AR4-AUC30, respectively). Bleeding events occurred in 43 patients during a 22-month follow-up. AR4-AUC30was significantly lower in patients with bleeding events than in those without (584 [96-993] vs. 1,028 [756-1,252], P=0.0003). Multivariate logistic regression analysis identified AR4-AUC30(odds ratio 3.18) as a significant predictor of bleeding events, in addition to baseline anemia and usage of the standard dose of direct oral anticoagulants. However, PL18-AUC10was not significantly related to bleeding events. CONCLUSIONS: A lower AR4-AUC30level was associated with increasing risk of subsequent bleeding complications in patients with stable coronary artery disease who received multiple antithrombotic agents.

Biodegradable Injectable Polymer Systems Exhibiting Temperature-Responsive Irreversible Sol-to-Gel Transition by Covalent Bond Formation.

Biodegradable injectable polymer (IP) systems exhibiting temperature-responsive sol-to-gel transitions between room temperature and body temperature have the potential for use in biomedical applications. However, gelation of such IP systems is a reversible process through physical cross-linking, and the hydrogels thus formed are likely to revert to the sol state under highly wet conditions after injection. In this study, a biodegradable IP system exhibiting temperature-responsive irreversible sol-to-gel transition by covalent bond formation was developed by simple mixing of polymers. A triblock copolymer of poly(caprolactone-co-glycolic acid) and poly(ethylene glycol) (tri-PCG) and tri-PCG with attached succinimide ester groups at both termini (tri-PCG-SA-OSu) were prepared and mixed together with a water-soluble polyamine (typically poly-l-lysine). The obtained IP formulation was in the sol state after mixing, but exhibited a rapid sol-to-gel transition within 30 s upon increasing the temperature to 37 °C. Once formed, the hydrogel did not revert to the sol state, even after cooling to 4 °C, because of the formation of covalent bonds upon transition. The obtained hydrogel soaked in phosphate buffered saline (PBS) exhibited a significantly longer duration time of the gel state. This IP system exhibiting a rapid and irreversible sol-to-gel transition is convenient for medical professionals and possesses great potential for use in biomedical devices for clinical applications such as drug delivery systems and antiadhesive materials.

Pharmacodynamic Assessment of Platelet Reactivity After a Loading Dose of Prasugrel or Clopidogrel in Patients With ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Few studies have compared the platelet reactivity of prasugrel and clopidogrel in the acute phase of ST-segment elevation myocardial infarction (STEMI).Methods and Results:Primary percutaneous coronary intervention (PCI) was performed in 78 patients with STEMI within 12 h of onset. Patients were randomly assigned to receive a Japanese standard loading dose of prasugrel 20 mg or clopidogrel 300 mg. Platelet reactivity was serially assessed using the VerifyNow-P2Y12 assay, the results of which were expressed as P2Y12-reaction-units (PRU). PRU values were significantly lower in the prasugrel group (n=38) than in the clopidogrel group (n=40) at 3 h, 24 h, and 14 days after loading (191±101 vs. 271±50, 147±80 vs. 261±57, and 171±67 vs. 221±70, respectively, P<0.05), although the PRU levels at baseline (231±57 vs. 237±58, P=0.65) and 1 h after loading (282±65 vs. 291±62, P=0.54) were similar. As compared with the baseline values, the PRU levels at 1, 3 and 24 h after clopidogrel loading were significantly higher (respectively, P<0.05), whereas only the PRU at 1 h after prasugrel was elevated (P<0.001). CONCLUSIONS: In Japanese patients with STEMI who undergo primary PCI, prasugrel provides stronger platelet inhibition than clopidogrel from 3 h after loading, whereas platelet reactivity remained elevated within 24 h after clopidogrel loading. (Circ J 2016; 80: 2520-2527).

Introduction of an examination and treatment for Helicobacter pylori infection in high school health screening.

BACKGROUND: Recently, a significant relationship between gastric cancer and Helicobacter pylori infection has been proven. The purpose of this study was to elucidate the actual conditions of H. pylori infection in Japanese teenagers. METHODS: The study subjects were students at a certain high school between 2007 and 2009. They were first examined with a urinary rapid test kit based on immunochromatographic technology [corrected] for detection of the antibody to H. pylori (RAPIRAN®). [corrected]. Students who tested positive on this screening examination visited Shinshu University Hospital and received esophagogastroduodenoscopy, and biopsy samples were taken to examine their H. pylori status. The resolution of H. pylori infection was assessed by urea breath test. RESULTS: For 3 years, 1,224 of 1,232 students (99.4%) received a screening examination for H. pylori infection. Sixty-four of these 1,224 students (5.2%) were found to be positive for H. pylori. Thirty of these 64 H. pylori-positive students visited our hospital, and 24 of them (80%) were confirmed to be infected by H. pylori. The most common endoscopic findings for students with H. pylori infection were nodular gastritis (58.3%) and closed-type atrophic gastritis (45.8%). Histological findings showed no evidence of intestinal metaplasia, except in one of the students. All 24 students were successfully cured of H. pylori infection. If this procedure were to be introduced into the nationwide health screening at Japanese high schools, we calculated that the cost of the prevention of a gastric cancer would be 454,073 yen for each person. CONCLUSIONS: The low rate of prevalence of H. pylori infection in Japanese teenagers would make it possible to perform examinations and carry out treatment for this infection in high school health screenings from the standpoint of medical economy.

Small bowel tissue concentration of rebamipide: study of two dosages in healthy subjects.

Non-steroidal anti-inflammatory drug (NSAID)-related small intestinal complications exist, since developed new diagnostic modalities, such as balloon and capsule endoscopies. Some experiments have shown rebamipide to protect from NSAID-induced small intestinal complications. The purpose of this study is to investigate whether the effective concentrations of rebamipide (COR) are present in the small intestine after taking an ordinary clinical dose and double dose of this drug. Twelve healthy male subjects were enrolled. After taking 100 or 200 mg of rebamipide, balloon enteroscopy was performed at 1 and 3 h, and biopsy samples were obtained from the jejunum and the stomach. Venous blood samples were taken simultaneously. Samples were analyzed by high-performance liquid chromatography. The mean COR in the jejunum was higher than 100 µM at 1 h and higher than 10 µM at 3 h in both the 100 and 200 mg groups. Mean COR in the stomach was less than 100 µM at 1 h in the 100 mg group; however it was higher than 100 µM in the 200 mg group. In conclusion, the COR level in the jejunum was sufficient to protect for NSAID-induced gastrointestinal complications.