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The association between the pharmacokinetics and pharmacodynamics of regorafenib, a multiple tyrosine kinase inhibitor, remains unclear. This study assessed the trough plasma concentrations (Ctrough) of regorafenib and its N-oxide (M2) and N-oxide/desmethyl (M5) metabolites, and evaluated the associations among these levels, adverse events, and pharmacokinetic-related genetic polymorphisms in patients with metastatic colorectal cancer. The Ctrough levels of regorafenib and its metabolites were assessed in a single-center, prospective, observational study, 7 days after the initial treatment. The correlation between those values and adverse events was then examined. In addition, the genetic polymorphisms of ABCG2, SLCO1B1, and UGT1A9 were determined and evaluated for associations with the levels of regorafenib, M2, and M5. We analyzed 43 patients who received regorafenib 40–120 mg/day; among them, 35 patients started at 120 mg/day. With regard to bilirubin increase, the Ctrough values of regorafenib were significantly higher in the group with grade ≥ 2 than in groups with grades 0 and 1 (p = 0.010). The M5 Ctrough levels were significantly associated with the severity of hypertension or rash (p

Background The carriage prevalence of pneumococcus among community-dwelling older adults is not fully understood, especially in superaged societies. Our purpose was to elucidate the carriage prevalence of pneumococcus in the upper respiratory tract among Japanese community-dwelling adults aged ≥65 years. Methods We conducted a cross-sectional study of generally healthy community-dwelling adults aged ≥65 years in Nagasaki city, Japan. Demographic and clinical data and nasopharyngeal, oropharyngeal and saliva samples were collected from February 21st, 2018, to December 17th, 2018. The specimens were tested by culture and molecular methods. Results Among a total of 504 enrolled participants, none were positive for pneumococcus by culture, and 22 were positive by PCR. The overall carriage prevalence was 4.4% (95% CI: 2.8–6.5%). The prevalence was highest in saliva samples, followed by oropharyngeal and nasopharyngeal samples. No demographic characteristics were associated with carriage prevalence, including age (4.7% among participants aged 65–74 years and 4.1% among those 75 years and older). Among the pneumococcal-positive participants, 18.2% were PCV13-covered serotypes. Conclusions Our data suggest a low carriage prevalence of S. pneumoniae among community-dwelling older people in Japan.

Background Laboratory facilities for etiological diagnosis of central nervous system (CNS) infection are limited in developing countries; therefore, patients are treated empirically, and the epidemiology of the pathogens is not well-known. Tubercular meningitis is one of the common causes of meningitis, which has high morbidity and mortality, but lacks sensitive diagnostic assays. The objectives of this study were to determine the causes of meningitis in adult patients by using molecular assays, to assess the risk factors associated with them, and to explore whether biomarkers can differentiate tubercular meningitis from bacterial meningitis. Methods We conducted a cross-sectional study in the Department of Infectious Diseases, Bach Mai Hospital, Hanoi, Vietnam, from June 2012 to May 2014. All patients who were ≥ 16 years old and who had meningoencephalitis suggested by abnormal cerebrospinal fluid (CSF) findings (CSF total cell >5/mm3 or CSF protein ≥40 mg/dL) were included in the study. In addition to culture, CSF samples were tested for common bacterial and viral pathogens by polymerase chain reaction (PCR) and for biomarkers: C-reactive protein and adenosine deaminase (ADA). Results Total number of patients admitted to the department was 7506; among them, 679 were suspected to have CNS infection, and they underwent lumbar puncture. Five hundred eighty-three patients had abnormal CSF findings (meningoencephalitis); median age was 45 (IQR 31–58), 62.6% were male, and 60.9% were tested for HIV infection. Among 408 CSF samples tested by PCR, out of them, 358 were also tested by culture; an etiology was identified in 27.5% (n=112). S. suis (8.8%), N. meningitis (3.2%), and S. pneumoniae (2.7%) were common bacterial and HSV (2.2%), Echovirus 6 (0.7%), and Echovirus 30 (0.7%) were common viral pathogens detected. M. tuberculosis was found in 3.2%. Mixed pathogens were detected in 1.8% of the CSF samples. Rural residence (aOR 4.1, 95% CI 1.2–14.4) and raised CSF ADA (≥10 IU/L) (aOR 25.5, 95% CI 3.1–212) were associated with bacterial meningitis when compared with viral meningitis; similarly, raised CSF ADA (≥10 IU/L) (aOR 42.2, 95% CI 2.0–882) was associated with tubercular meningitis. Conclusions Addition of molecular method to the conventional culture had enhanced the identification of etiologies of CNS infection. Raised CSF ADA (≥10 IU/L) was strongly associated with bacterial and tubercular meningitis. This biomarker might be helpful to diagnose tubercular meningitis once bacterial meningitis is ruled out by other methods.

Background Eosinophilic meningitis (EM) is a rare clinical syndrome caused by both infectious and noninfectious diseases. In tropical pacific countries, Angiostrongylus cantonensis is the most common cause. However, the EM definition varies in the literature, and its relation to parasitic meningitis (PM) remains unclear. Methodology/Principal findings Adult and adolescent patients of 13 years old or above with suspected central nervous system (CNS) infections with abnormal CSF findings were prospectively enrolled at a tertiary referral hospital in Hanoi, Vietnam from June 2012 to May 2014. Patients with EM or suspected PM (EM/PM) were defined by the presence of either ≥10% eosinophils or an absolute eosinophil cell counts of ≥10/mm3 in the CSF or blood eosinophilia (>16% of WBCs) without CSF eosinophils. In total 679 patients were enrolled: 7 (1.03%) had ≥10% CSF eosinophilia, 20 (2.95%) had ≥10/mm3 CSF eosinophilia, and 7 (1.03%) had >16% blood eosinophilia. The patients with ≥10% CSF eosinophilia were significantly younger (p = 0.017), had a lower body temperature (p = 0.036) than patients with ≥10/mm3 CSF eosinophilia among whom bacterial pathogens were detected in 72.2% (13/18) of those who were tested by culture and/or PCR. In contrast, the characteristics of the patients with >16% blood eosinophilia resembled those of patients with ≥10% CSF eosinophilia. We further conducted serological tests and real-time PCR to identify A. cantonensis. Serology or real-time PCR was positive in 3 (42.8%) patients with ≥10% CSF eosinophilia and 6 (85.7%) patients with >16% blood eosinophilia without CSF eosinophils but none of patients with ≥10/mm3 CSF eosinophilia. Conclusions The etiology of PM in northern Vietnam is A. cantonensis. The eosinophil percentage is a more reliable predictor of parasitic EM than absolute eosinophil count in the CSF. Patients with PM may present with a high percentage of eosinophils in the peripheral blood but not in the CSF., Author summary Eosinophilic meningitis (EM) is a rare meningitis accompanied by eosinophils in the CSF and caused by multiple etiologies. Angiostrongylus cantonensis, which is a rat lungworm parasite, is the most common cause in tropical Asia. Previous papers have defined EM as CSF eosinophils ≥10% or CSF eosinophils ≥10/mm3. However, the relationship of EM to parasitic meningitis (PM) remains unclear. This prospective study enrolled 679 patients with suspected CNS infection who were admitted to a tertiary referral hospital in Hanoi, Vietnam from June 2012 to May 2014. The characteristics of patients with ≥10% CSF eosinophilia resembled those of patients with >16% blood eosinophilia without CSF eosinophils, whereas those of patients with ≥10/mm3 CSF eosinophilia were comparable with those of patients with typical bacterial meningitis. Serology or real-time PCR for A. cantonensis was positive in 3 out of 7 patients with ≥10% CSF eosinophilia and 6 out of 7 patients with > 16% blood eosinophilia without CSF eosinophils but none of patients with ≥10/mm3 CSF eosinophilia. The percentage, in contrast to the absolute eosinophil count in CSF, is reliable for predicting parasitic EM. Patients with PM may present with eosinophilia in the peripheral blood but not in the CSF.