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1.
Gan To Kagaku Ryoho ; 46(8): 1259-1263, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501367

RESUMO

We retrospectively analyzed adverse effects(AEs), overall survival(OS), and progression-free survival(PFS)in 15 consecutive patients treated with FOLFIRINOX as the first-line treatment for recurrent or unresectable pancreatic ductal adenocarcinoma( PDAC)between February 2014 and December 2017 in our hospital. Eleven patients were treated for unresectable PDAC with distant metastases(UR-M), and 4 were treated for locally advanced unresectable PDAC(UR-LA). The median age was 56(range: 40-75)years. Nine patients were male, and 6 were female. The performance status was 0 or 1 in all patients. Tumors were located in the pancreas head in 8 cases and in the body-tail in 7 cases. Grade 5 AEs were observed in 1 case in which liver abscess causing sepsis resulted in mortality. The response rate was 20.0%, and the disease control rate was 66.7%. Two patients underwent conversion surgery after FOLFIRINOX treatment. Seven patients received a nab-paclitaxel plus gemcitabine regimen as second-line treatment. The median OS and PFS were 17.0 and 8.4 months, respectively, and the 1-year survival rate was 66.7%. FOLFIRINOX for recurrent and unresectable PDAC showed relatively good tumor control. However, strict attention is required for severe AEs. Conversion surgery might be effective in patients who are good responders even if they have metastatic disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas , Adulto , Idoso , Carcinoma Ductal Pancreático , Feminino , Fluoruracila , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Retrospectivos
2.
PLoS One ; 14(7): e0219819, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31310615

RESUMO

Rapid identification of causative agents from positive blood culture media is a prerequisite for the timely targeted treatment of patients with sepsis. The GENECUBE (TOYOBO Co., Ltd.) is a novel, fully-automated gene analyzer that can purify DNAs and amplify target DNAs. In this study, we evaluated the ability of two newly developed GENECUBE assays to directly detect the nuc and mecA genes in blood culture medium; nuc is specific to Staphylococcus aureus, and mecA indicates methicillin resistance. We examined 263 positive blood culture samples taken at three hospitals from patients suspected of having staphylococcal bacteremia. The results were then compared with those obtained using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, antimicrobial susceptibility testing (Microscan system or Dry-plate EIKEN), and sequencing analysis. The GENECUBE assays had sensitivity and specificity of 100% in detecting both S. aureus and methicillin resistance in positive blood culture. The turnaround time of the examination was evaluated for 36 positive blood culture samples. The time between the initiation of incubation and completion of the GENECUBE examination was 23 h (interquartile range: IQR 21-37 h); the time between reporting of Gram stain examination and completion of the GENECUBE examination was 52 min (IQR 48-62 min). These findings show that the GENECUBE assays significantly reduce the assay time with no loss of sensitivity or specificity.

3.
Cancer Med ; 8(10): 4883-4891, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31231974

RESUMO

This multicenter, prospective, observational cohort study assessed opioid induced constipation (OIC) in Japanese patients with cancer. Eligible patients had stable cancer and an ECOG PS of 0-2. OIC incidence based on the Rome IV diagnostic criteria was determined by patient diary entries during the first 14 days of opioid therapy. The proportion of patients with OIC was calculated for each 1-week period and the overall 2-week study period. Secondary measurements of OIC included the Bowel Function Index (BFI) score (patient assessment administered by physician), spontaneous bowel movements (SBMs) per week (patient assessment), and physician assessments. Medication for constipation was allowed. Two hundred and twenty patients were enrolled. The mean morphine-equivalent dose was 22 mg/day. By Rome IV criteria, the cumulative incidence of OIC was 56% (95% CI: 49.2%-62.9%); week 1, 48% (95% CI: 40.8%-54.6%); week 2, 37% (95% CI: 30.1%-43.9%). The cumulative incidence of OIC was lower in patients who received prophylactic agents for constipation (48% [95% CI: 38.1%-57.5%]) than in patients who did not (65% [95% CI: 55.0%-74.2%]). The cumulative incidences of OIC were 59% (95% CI: 51.9%-66.0%), 61% (95% CI: 54.3%-68.1%), and 45% (95% CI: 38.0%-51.8%) based on BFI scores, physician assessments, and SBM frequency, respectively. Frequency of BMs/week before starting opioids was the most influential factor for the occurrence of OIC. Utilization of prophylactic agents for constipation was associated with a modest effect on reducing the incidence of OIC. The incidences of OIC reported were variable depending on the diagnostic tool involved.

4.
J Infect Chemother ; 25(8): 578-583, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30905631

RESUMO

Recently, rapid molecular detection systems have been used for point-of-care testing for the diagnosis of influenza worldwide. Here, we evaluated the performance of the cobas Liat system and the cobas Influenza A/B assay (Liat) using fresh nasopharyngeal samples collected from a Japanese population between December 2017 and February 2018. The performance of the examination was compared with that of antigen testing and a conventional polymerase chain reaction (nested-PCR) method. A total of 159 patients were included in this study, and 77 tested positive using Liat. The concordance rate between Liat and nested PCR was 97.5%. The median time between the ordering of testing and completion of molecular analyses using Liat was 30 min (interquartile range: 28-35 min). The overall sensitivity and specificity of antigen testing were 57.1% and 100%, respectively. The duration from symptom onset to examination did not alter antigen testing sensitivity. The current study demonstrates the high performance of Liat for the rapid molecular identification of the influenza virus.

5.
Anticancer Res ; 39(1): 413-420, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30591488

RESUMO

BACKGROUND: Patients with adenocarcinoma of the lung are routinely screened for anaplastic lymphoma kinase (ALK) rearrangement because they can be treated by ALK-specific targeted therapy. The clinical and molecular characteristics of large-cell neuroendocrine carcinoma (LCNEC) associated with ALK rearrangement are still unclear. Herein, we assessed the ALK status in a series of patients with LCNEC by testing methods commonly used for adenocarcinoma. MATERIALS AND METHODS: ALK expression was first examined by immunohistochemistry. For a positively stained tumor, molecular analyses were then conducted. The ALK fusion partner found in a patient with ALK rearrangement was further identified by direct DNA sequencing. Patient clinicopathological features were also analyzed, focusing on the ALK rearrangement-positive case. RESULTS: Immunohistochemistry of seven patients identified strong ALK expression in one case of stage IV LCNEC. Molecular analysis identified a novel rearranged gene resulting from the fusion of kinesin family member 5B (KIF5B) exon 17 to ALK exon 20. The patient was treated with ALK-specific inhibitors, crizotinib and later, alectinib, and has remained alive for more than 24 months without disease progression. Three of the remaining six patients without ALK rearrangement had stage IV cancer and received cytotoxic chemotherapies. Their average overall survival was 5.4 months. CONCLUSION: To our knowledge, this is the first report of a KIF5B-ALK fusion gene in LCNEC. The patient was successfully treated with ALK inhibitors, suggesting that sensitivity to ALK inhibitor may define a specific LCNEC subtype. We propose that screening for ALK rearrangement in patients with LCNEC may assist in selecting potential candidates for targeted therapy.


Assuntos
Quinase do Linfoma Anaplásico/genética , Carcinoma de Células Grandes/genética , Carcinoma Neuroendócrino/genética , Proteínas de Fusão Oncogênica/genética , Adulto , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma de Células Grandes/patologia , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Rearranjo Gênico/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Inibidores de Proteínas Quinases/administração & dosagem
6.
Tohoku J Exp Med ; 246(4): 225-231, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30541996

RESUMO

Mycoplasma pneumoniae is a leading causative pathogen of pneumonia among pediatric patients, and its accurate diagnosis may aid in the selection of appropriate antimicrobial agents. We established a rapid reporting system of a polymerase chain reaction (PCR) examination for M. pneumoniae that enables physicians to obtain test results approximately 90 minutes after ordering the test. In this study, we evaluated the impact of this system on antimicrobial prescriptions for pediatric pneumonia patients after its implementation from May 2016 to April 2017. In total, we identified 375 pediatric pneumonia patients, and the results of the rapid PCR examinations for Mycoplasma pneumoniae were reported immediately in 90.7% of patients (340/375), with physicians able to use these results to decide on patients' management before the prescription of antimicrobial agents. Of the 375 pediatric pneumoniae patients, M. pneumoniae was detected in 223 (59.5%). Among the 223 M. pneumoniae-positive pneumonia cases, antimicrobial agents for atypical pathogens (macrolides, tetracyclines or quinolones) were prescribed in 97.3% (217/223) at the initial evaluation, and their prescription rates increased to 99.1% (221/223) during management. In contrast, antimicrobial agents for atypical pathogens were prescribed only in 10.5% of 152 M. pneumoniae-negative pneumonia cases at the initial evaluations, and only 1 additional case was prescribed clarithromycin for persistent symptoms during management. In conclusion, we show that molecular technology could be applicable in the field of point-of-care testing in infectious disease, and its implementation will ensure the correct antimicrobial prescription for pediatric pneumonia patients.


Assuntos
Antibacterianos/uso terapêutico , Prescrições de Medicamentos , Mycoplasma pneumoniae/isolamento & purificação , Patologia Molecular/métodos , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Sistemas Automatizados de Assistência Junto ao Leito , Adolescente , Antibacterianos/farmacologia , Criança , Feminino , Humanos , Macrolídeos/farmacologia , Macrolídeos/uso terapêutico , Masculino , Quinolonas/farmacologia , Quinolonas/uso terapêutico , Tetraciclina/farmacologia , Tetraciclina/uso terapêutico , Fatores de Tempo
7.
J Gen Fam Med ; 19(6): 191-197, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30464865

RESUMO

Background: Mycoplasma pneumoniae is a common pathogen causing pneumonia; macrolide-resistant strains are rapidly spreading across Japan. However, the clinical features of macrolide-resistant M. pneumoniae pneumonia have not been well established. Here, we evaluated the clinical characteristics and seasonal variations in the prevalence of M. pneumoniae with macrolide-resistant mutations (MRM). Methods: The monthly prevalence of MRM in M. pneumoniae strains isolated from May 2016 to April 2017 was retrospectively analyzed, and the clinical characteristics of pneumonia cases with MRM were compared to those of cases without MRM. The M. pneumoniae isolates and point mutations at site 2063 or 2064 in domain V of 23S rRNA were evaluated by the GENECUBE system and GENECUBE Mycoplasma detection kit. Results: Mycoplasma pneumoniae infection was identified in 383 cases, including 221 cases of MRM (57.7%). The MRM prevalence was 86.3% (44/51) between May and July 2016, demonstrating an apparent decrease in September 2016, subsequently reaching 43.0% (34/79) in November 2016. Mycoplasma pneumoniae pneumonia was diagnosed in 275 cases, including 222 pediatric and 53 adult cases. Macrolide use preceding evaluation was found to be the only feature of MRM pneumonia cases both in children (odds ratio [OR] 3.86, 95% confidence interval [CI]:1.72-8.66) and in adults (OR 7.43, 95% CI: 1.67-33.1). Conclusions: The determination rate of MRM varied widely throughout the year, and our study demonstrated the challenges in predicting M. pneumoniae with MRM based on clinical features at diagnosis. Therefore, continuous monitoring of the prevalence of MRM is warranted, which may help in selecting an effective treatment.

8.
J Infect Chemother ; 24(12): 998-1003, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30007866

RESUMO

An 83-year-old previously self-sufficient man was referred to our hospital for a fever, severe tenderness over the lumbar spine, and elevated C-reactive protein levels. Computed tomography revealed fluid collection in the intervertebral space of L3/4. Gram-positive, short rod-shaped bacteria were isolated from two sets of blood cultures. A 16S rRNA sequence analysis of an isolate showed a similarity of 98.1% to the nearest type strain Brachybacterium squillarum JCM 16464T. Biochemical characteristics of the presently isolated strain differed from those of the most closely related species of the genus Brachybacterium. The patient was successfully discharged on day 73 of admission with antimicrobial therapies and showed no recurrence during outpatient visits. Brachybacterium spp. have mainly been isolated from the environment, and human Brachybacterium infections have rarely been documented to date. To our knowledge, this is the first clinical isolation of Brachybacterium sp. as a causative pathogen of bloodstream infection.

9.
J Nutr Sci Vitaminol (Tokyo) ; 64(3): 209-214, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29962432

RESUMO

The association between advanced age and the thiamine concentration has not been conclusively determined. A recent report from Japan showed that more than half of nursing home elderly residents at an institution had a low whole-blood thiamine concentration (<20 ng/mL). Therefore, a high incidence of low thiamine concentrations among hospitalized elderly has been anticipated in the Japanese population but never investigated. We evaluated the whole thiamine concentration in newly hospitalized elderly patients (≥65 y old) with infectious diseases. Evaluations were performed on admission and at days 6-8 of hospitalization with liquid chromatography tandem mass spectrometry (LC/MS/MS). As a result, we enrolled a total of 471 patients from September 2015 to December 2016. The median thiamine concentration was 46 ng/mL (IQR, 37-58 ng/mL). Only 7 patients (1%) had thiamine concentrations below 20 ng/mL (66 nmol/L) on admission. Five of these patients were bedridden and unable to eat food by themselves, and the other two patients used loop diuretics for chronic heart failure. The thiamine concentration declined in most patients (84%) at days 6-8 of admission, regardless of their dietary intake during hospitalization. In conclusion, a low thiamine concentration was not prevalent among newly hospitalized elderly patients with infectious diseases. However, the thiamine concentration significantly decreased during the 6-8 d of hospitalization.


Assuntos
Envelhecimento/sangue , Hospitalização , Infecção/sangue , Tiamina/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais Comunitários/estatística & dados numéricos , Humanos , Japão/epidemiologia , Masculino , Deficiência de Tiamina/epidemiologia
10.
Intern Med ; 54(11): 1437-40, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26028003

RESUMO

A 43-year-old man was referred to our hospital for an acute-onset fever and left flank pain. He had been previously diagnosed with lymphangioma, and abdominal computed tomography showed pararenal cysts with fat stranding around the left kidney, of which infection was subsequently confirmed on magnetic resonance imaging. Gram-negative spiral bacilli were isolated from two sets of blood cultures, and Helicobacter cinaedi was identified using 16S rRNA sequencing. The patient was successfully treated with ceftriaxone therapy without recurrence. A multilocus sequence typing analysis indicated the current H. cinaedi strain differed from previous strains isolated in Japan.


Assuntos
Bacteriemia/diagnóstico , Infecções por Helicobacter/diagnóstico , Linfocele/diagnóstico , Adulto , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Ceftriaxona/uso terapêutico , Helicobacter/genética , Helicobacter/isolamento & purificação , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Humanos , Japão , Linfocele/diagnóstico por imagem , Masculino , Tipagem de Sequências Multilocus , RNA Ribossômico 16S/genética , Radiografia
11.
Oncotarget ; 5(8): 2293-304, 2014 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-24810493

RESUMO

Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from advanced NSCLC patients enrolled in LETS phase III trial comparing first-line S-1/carboplatin with paclitaxel/carboplatin and subjected to multiplex genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel) with the Sequenom MassARRAY platform. MET amplification was evaluated by fluorescence in situ hybridization. A somatic mutation in at least one gene was identified in 48% of non-squamous cell carcinoma and 45% of squamous cell carcinoma specimens, with EGFR (17%), TP53 (11%), STK11 (9.8%), MET (7.6%), and KRAS (6.2%). Mutations in EGFR or KRAS were associated with a longer or shorter median overall survival, respectively. The LungFusion Panel identified ALK fusions in six cases (2.5%), ROS1 fusions in five cases (2.1%), and a RET fusion in one case (0.4%), with these three types of rearrangement being mutually exclusive. Nine (3.9%) of 229 patients were found to be positive for de novo MET amplification. This first multiplex genotyping of NSCLC associated with a phase III trial shows that MassARRAY-based genetic testing for somatic mutations and fusion genes performs well with nucleic acid derived from FFPE specimens of NSCLC tissue.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Pulmonares/genética , Reação em Cadeia da Polimerase Multiplex/métodos , Adulto , Idoso , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Análise Mutacional de DNA , Combinação de Medicamentos , Feminino , Humanos , Hibridização in Situ Fluorescente , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Mutação , Ácido Oxônico/administração & dosagem , Paclitaxel/administração & dosagem , Tegafur/administração & dosagem
12.
Cancer Chemother Pharmacol ; 65(2): 243-50, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19479254

RESUMO

PURPOSE: D-19575 (glufosfamide: ß-D-glucosylisophosphoramide mustard) is an alkylating agent in which isophosphoramide mustard, the cytotoxic metabolite of ifosfamide, is covalently linked to ß-D-glucose. We have performed a phase I study to determine the safety profile, pharmacokinetics, and antitumor activity of D-19575 in Japanese patients with advanced solid tumors METHODS: Patients were treated with escalating doses of D-19575 administered by a two-step (fast-slow) intravenous infusion over 6 h every 3 weeks. Thirteen patients received 43 treatment cycles (median 3; range 1-11) at D-19575 doses of 3,200, 4,500, or 6,000 mg/m(2). RESULTS: Hematologic toxicities and other side effects were generally mild. The maximum tolerated dose of D-19575 was 6,000 mg/m(2), at which two patients experienced dose-limiting toxicities (hypophosphatemia, hypokalemia, and metabolic acidosis each of grade 3). Pharmacokinetic analysis revealed a linear relation between the area under the concentration-versus-time curve (AUC) and dose. The AUC values for isophosphoramide mustard were substantially greater than those achieved by bolus administration or continuous infusion of ifosfamide in conventional therapy. One patient with gallbladder cancer previously treated with cisplatin and gemcitabine achieved a partial response lasting for >5 months, and eight patients achieved disease stabilization. CONCLUSIONS: Our results show that D-19575 can be safely administered by infusion over 6 h at 4,500 mg/m(2) every 3 weeks. The safety profile and potential antitumor activity of D-19575 show that phase II studies of this drug are warranted.


Assuntos
Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Mostardas de Fosforamida/farmacocinética , Mostardas de Fosforamida/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Feminino , Glucose/análogos & derivados , Humanos , Ifosfamida/análogos & derivados , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Mostardas de Fosforamida/efeitos adversos , Tomografia Computadorizada por Raios X
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