Anti-factor Xa activity, prothrombin time, and activated partial thromboplastin time in patients treated with factor Xa inhibitors.

The regimens for factor Xa (FXa) inhibitors (apixaban, edoxaban, and rivaroxaban) vary with venous thromboembolism (VTE) or non-valvular atrial fibrillation (NVAF). The dosage and duration of FXa inhibitor therapy also differ. However, the distribution of anti-factor Xa activity (AXA) values, prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients administered each FXa inhibitor has not fully been assessed. Trough and peak AXA values, PT, and APTT were measured in 85 patients taking apixaban, 105 patients taking edoxaban, and 27 patients taking rivaroxaban. The patients were further divided into three groups based on the dosage. Each FXa inhibitor showed various ranges of AXA values, and twice-daily use resulted in higher absolute AXA values than once-daily use. AXA values and PT for 20 mg apixaban at both trough and peak times were significantly higher than those for 5 mg or 10 mg. AXA values for 60 mg edoxaban at peak time were significantly higher than those for 15 mg or 30 mg. AXA values for 30 mg of rivaroxaban at both trough and peak times were significantly higher than those for 10 mg or 15 mg. In a nonlinear regression model of the relationship between AXA and PT or APTT, PT was positively correlated with AXA values for each FXa inhibitor. This study obtained trough and peak levels of AXA, PT, and APTT in patients with VTE or NVAF who were administered apixaban, edoxaban, and rivaroxaban.

Impact of Renal Function on Anti-factor Xa Activity Concentrations with Edoxaban Use in Patients with Non-valvular Atrial Fibrillation.

BACKGROUND: Chromogenic anti-factor Xa activity (AXA) assay is used to measure the pharmacodynamics of factor Xa inhibitors, including edoxaban. Although AXA concentrations in patients with non-valvular atrial fibrillation using edoxaban have been reported, the impact of renal function on AXA concentrations with edoxaban use in patients with non-valvular atrial fibrillation has not been fully assessed. METHODS: Trough and peak AXA concentrations were measured in 93 patients with non-valvular atrial fibrillation taking edoxaban (73.6 ± 11.2 years, 48 were male). The patients were divided into three groups: patients with moderate renal dysfunction (creatinine clearance 15-49 mL/min), mild renal dysfunction (creatinine clearance 50-95 mL/min), and normal renal function (creatinine clearance > 95 mL/min). Both trough and peak AXA concentrations were assessed among the groups according to the edoxaban dose (30 or 60 mg). RESULTS: At a 30-mg dose, patients with moderate renal dysfunction showed significantly higher trough AXA concentrations than patients with mild renal dysfunction or normal renal function. At a 60-mg dose, patients with mild renal dysfunction showed significantly higher trough AXA concentrations than patients with normal renal function. Peak AXA concentrations were not significantly different between the groups. Creatinine clearance was significantly and negatively correlated with trough AXA concentrations at a 60-mg dose, whereas the correlation of creatinine clearance with AXA concentrations was borderline significant at a 30-mg dose. No correlation was found between creatinine clearance and peak AXA concentrations at either dose. CONCLUSIONS: Creatinine clearance tends to be negatively correlated with trough AXA concentrations in patients with non-valvular atrial fibrillation taking edoxaban, while renal function is not correlated with peak AXA concentrations.

Coagulation markers in patients with venous thromboembolism treated with 10 mg apixaban twice daily.

Apixaban is used to treat venous thromboembolism (VTE) at 10 mg twice daily (BID) for 7 days, followed by 5 mg BID without dose adjustment, and non-valvular atrial fibrillation (NVAF) at 5 mg BID or 2.5 mg BID with dose adjustment criteria (DAC) including age, body weight, and renal function. The anti-factor Xa activity (AXA), prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients with VTE receiving 10 mg BID of apixaban remains unclear. Twenty-six patients (70.8±15.4 years, 10 males) with VTE receiving 10 mg BID of apixaban were enrolled. The patients were divided into two groups based on whether they met the DAC of NVAF: DAC group (n=8) and non-DAC group (n=18). Trough and peak AXA values, PT, and APTT were measured at 10 mg BID dosage and then at 5 mg BID dosage. Coagulation markers in recipients of 10 mg BID therapy were significantly higher than those of 5 mg BID recipients. A significant and strong positive correlation was observed between AXA and PT at trough and peak times. The AXA values and PT in the DAC group were significantly higher than those in the non-DAC group. No significant inter-group differences were seen in APTT. This study provides the first report of AXA distribution in VTE patients receiving 10 mg BID of apixaban. Our findings indicate that coagulation markers may differ in patients with VTE-prescribed higher doses of apixaban and a DAC may be warranted in such patients.

An Adult Case of Herpes Simplex Virus-associated Granulomatous Encephalitis.

Brain granuloma occurs under certain conditions. Herpes simplex virus (HSV) causes granulomatous encephalitis in children; however, it has been rarely reported in adults. A 74-year-old man with a history of herpes simplex encephalitis suffered recurrent seizures. Brain magnetic resonance imaging revealed a mass lesion and resection was performed. A polymerase chain reaction using a brain biopsy specimen was positive for HSV DNA; thus, the patient was diagnosed with HSV-associated granulomatous encephalitis. After administering acyclovir, the patient showed improvement. HSV can cause granulomatous encephalitis in adults, and acyclovir can be used for its treatment.

Progressive Multifocal Leukoencephalopathy Localized in the Cerebellum and Brainstem Associated with Idiopathic CD4(+) T Lymphocytopenia.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that favors the cerebrum and typically occurs in immunosuppressed patients. We herein report the case of a 66-year-old man with PML, idiopathic CD4(+) T lymphocytopenia (ICL), and chronic renal failure. Cranial magnetic resonance imaging (MRI) showed a crescent-shaped lesion in the left cerebellum, brainstem, and middle cerebellar peduncle. Although the patient did not present with HIV infection, collagen diseases, or tumors, JC virus DNA was detected in the cerebrospinal fluid. Clinicians should consider PML and ICL in the differential diagnosis if the patient develops progressive ataxia and a crescent-shaped cerebellar lesion on MRI.

Intracerebral hemorrhage in patients after heart valve replacement.

BACKGROUNDS: Although prevention of hematoma enlargement and thromboembolic complications is critically important in acute intracerebral hemorrhage (ICH) patients with prosthetic heart valves, clinical data are scarce. The goal of this study was to elucidate patient characteristics, acute treatments, and the clinical course of them. METHODS: We investigated a retrospective cohort of consecutive acute ICH patients with prosthetic heart valves. Neurological data, hospital management, hemorrhagic and thromboembolic complications and functional disability/mortality were reviewed. RESULTS: We identified 38 patients (27 men; 67.9±16.7 years). The median ICH volume was 22.8 ml. The most frequent location was lobar (50%). All patients with mechanical valves (25/25) and 46% of patients with bioprosthetic valves (6/13) were receiving warfarin at the time of hospital admission. The median anticoagulation withholding period was 2 days in 24 patients who ultimately resumed anticoagulation. Hematoma enlargement within 24 h was observed in eight patients and hemorrhagic complications occurred in three patients. Thromboembolic stroke occurred in four patients. At discharge, death had occurred or severe disability was present in 53% of patients (20/38). CONCLUSIONS: Hematoma enlargement, hemorrhagic complications or thromboembolic stroke occurred in a significant number of patients during hospitalization. ICH was a serious complication among patients with valve replacement.

Seizure Outcomes and Predictors of Recurrent Post-Stroke Seizure: A Retrospective Observational Cohort Study.

BACKGROUND: Seizure is a common complication after stroke (termed "post-stroke seizure," PSS). Although many studies have assessed outcomes and risk factors of PSS, no reliable predictors are currently available to determine PSS recurrence. We compared baseline clinical characteristics and post-stroke treatment regimens between recurrent and non-recurrent PSS patients to identify factors predictive of recurrence. METHODS: Consecutive PSS patients admitted to our stroke center between January 2011 and July 2013 were monitored until February 2014 (median 357 days; IQR, 160-552) and retrospectively evaluated for baseline clinical characteristics and PSS recurrence. Cumulative recurrence rates at 90, 180, and 360 days post-stroke were estimated by Kaplan-Meier analysis. Independent predictors of recurrent PSS were identified by Cox proportional-hazards analysis. RESULTS: A total of 104 patients (71 men; mean age, 72.1 ± 11.2 years) were analyzed. PSS recurred in 31 patients (30%) during the follow-up. Factors significantly associated with PSS recurrence by log-rank analysis included previous PSS, valproic acid (VPA) monotherapy, polytherapy with antiepileptic drugs (AEDs), frontal cortical lesion, and higher modified Rankin Scale score at discharge (all p < 0.05). Independent predictors of recurrent PSS were age <74 years (HR 2.38, 95% CI 1.02-5.90), VPA monotherapy (HR 3.86, 95% CI 1.30-12.62), and convulsions on admission (HR 3.87, 95% CI 1.35-12.76). CONCLUSIONS: Approximately one-third of PSS patients experienced seizure recurrence within one year. The predictors of recurrent PSS were younger age, presence of convulsions and VPA monotherapy. Our findings should be interpreted cautiously in countries where monotherapy with second-generation AEDs has been approved because this study was conducted while second-generation AEDs had not been officially approved for monotherapy in Japan.

Radiographic conjugate horizontal eye deviation in patients with acute cerebellar infarction.

BACKGROUNDS: Conjugate eye deviation (CED) has not been fully investigated in patients with acute cerebellar infarction. We investigated the incidence of CED on neurological examination and head imaging with acute cerebellar infarction and associations of CED with the involved vascular territory, lesion site and other clinical factors. METHODS: We retrospectively reviewed clinical records and imaging in patients with acute cerebellar infarction within 12h after onset. We defined radiographic CED as deviation of each eye to the same side >10° on head imaging. RESULTS: Thirty-five patients with acute cerebellar infarction were identified (22 men; age range, 37-85 years). No patients showed CED on neurological examination, but 13 (37%) had radiographic CED, mostly contralateral to the lesion. As for infract location, the posterior inferior cerebellar artery (PICA) territory (44% vs. 20%, p=0.18) and flocculonodular lobe and/or vermis (54% vs. 32%, p=0.20) tended to be more involved in patients with radiographic CED than in those without. CONCLUSIONS: Radiographic CED seems relatively common in patients with acute cerebellar infarction, particularly the PICA territory infarcts including the flocculonodular lobe and/or vermis.

Early-onset dystonia after supplementary motor area infarction.

A 63-year-old patient with the right supplementary motor area infarct developed early-onset dystonia in the left upper extremity. The mechanisms involved in the genesis of focal dystonia are discussed with emphasis on cortical basal ganglia circuit and efferent projections from the supplementary motor area.

Antitussive effect of bakumondoto a fixed kampo medicine (six herbal components) for treatment of post-infectious prolonged cough: controlled clinical pilot study with 19 patients.

Bakumondoto (TJ-29) is a traditional herbal medicine that has been used in Japan for the treatment of bronchitis, bronchial asthma, and cough. This study investigated the effect of TJ-29 for the treatment of post-infectious prolonged cough. We performed a multicenter randomized controlled trial treating patients without (group A, n=11) or with TJ-29 (group B, n=8) for a total of 2 weeks using a beta 2 stimulant as the basal agent. Efficacy and safety were compared by a cough diary, VAS and sleeping questionnaire. At 4 and 5 days after treatment, the cough score of group B showed significant improvement compared with group A, demonstrating an early antitussive effect. At the assessment 2 weeks after treatment start, both groups showed similar levels of improvement in the cough score. No significant difference was observed in the VAS and the sleeping questionnaire items. In conclusion, oral TJ-29 administration could be useful and safe for the treatment of post-infectious prolonged cough.

[A DRG/PPS simulation in the medical care of tuberculosis].

PURPOSE: To study the expected usefulness of the introduction of the DRG-PPS (Diagnosis-Related Group/Prospective Payment System, in which an insurer pays a fixed medical fee per hospitalization) into the current medical care of tuberculosis (TB) in Japan. METHOD: The medical fees were reviewed for all TB inpatients at 19 hospitals under the National Hospital Organization who were discharged in either June 2007 or February 2008. The sum of the fixed fee by the DRG was assumed based on the bivariate regression analysis of each patient's hospital days and his or her total actual fees during the hospital stay under the current (fee for care) system, since it was difficult to directly calculate the daily fees for every patient that would be the basis of DRG-PPS. RESULTS: Linear regression analysis estimated that the medical fees (including fees for the medical examinations and the treatments) for a hospital stay of 60 days, which is the standard for TB treatment, was 1,192,470 yen (19,870 yen per person per day) in June 2007, and 1,167,600 yen (19,460 yen per person per day) in February 2008. DISCUSSION: If we assume an average medical fee of about Y1.1-1.2 million yen for the standard hospital care of TB, the economic balance of the hospitals is negative, with a deficit of 0.6-0.7 million yen, given the estimated expenses of 1.8 million yen (i.e., 30,000 yen per person per day x 60 days). CONCLUSION: If the DRG-PPS is to be implemented based on the current medical fee rating system, the hospital administrators could not accept its introduction to the TB medical care service as it is, because it may undermine the economic management of hospitals.

Docetaxel and cisplatin as second-line chemotherapy for advanced non-small cell lung cancer.

AIMS AND BACKGROUND: Docetaxel and cisplatin are both active against non-small cell lung cancer (NSCLC). This pilot study evaluated the efficacy and toxicity of docetaxel and cisplatin as second-line chemotherapy for patients with advanced NSCLC. PATIENTS AND METHODS: Eleven patients with advanced NSCLC who had no response to platinum-based treatment or had recurrence after a partial response were enrolled (2 stage III B, 9 stage IV; 8 men, 3 women). Median age was 58 years (range, 40 to 74 years). Seven patients had an Eastern Cooperative Oncology Group performance status of 0, and four had a performance status of 1. Four weeks or more after the end of previous therapy, all 11 patients received docetaxel 60 mg/m2 and cisplatin 80 mg/m2 on day 1 every four weeks. RESULTS: Two patients (18.2%) achieved a partial response,five (45.4%) patients had stable disease, and four (36.4%) patients showed progressive disease after initiation of second-line therapy. Median survival was 277 days. Median time to disease progression was 101 days, and the one-year survival rate was 36.4%. Hematological toxicities were moderate. Grade 3 and 4 leukocytopenia and neutropenia were observed in five (45.4%) patients. Grade 3 anemia occurred in one (9 .1%) patient. No severe non-hematological toxicities were observed except grade 3 nausea in two (18.2%) patients. CONCLUSIONS: The regimen of docetaxel and cisplatin has reasonable efficacy with moderate toxicity as second-line chemotherapy for patients with previously treated, advanced NSCLC.

Significance of serum uric acid in patients with chronic respiratory failure treated with non-invasive positive pressure ventilation.

PURPOSE: The aim of the study was to evaluate serum uric acid (UA) levels before and after non-invasive positive pressure ventilation (NPPV) to assess the utility of serum UA as an indicator of acute exacerbation of chronic respiratory failure (CRF) in patients treated with NPPV. METHODS: We analyzed change in the serum UA level in 29 patients with CRF due to restrictive thoracic disease and treated with NPPV. RESULTS: After NPPV therapy, PaO2 was significantly increased and PaCO2 was significantly decreased in all patients. Sixty-two percent of patients (18 of 29) showed a decreased serum UA/creatinine (Cr) ratio after NPPV therapy, but, overall, there was no significant change in serum UA/Cr (P=0.0688). The change in serum UA/Cr was not correlated with the changes in PaO2 and PaCO2 after NPPV. When we compared patients in whom serum UA/Cr decreased (n=18) with patients in whom serum UA/Cr did not decrease (n=11), there were significantly fewer patients who suffered CRF exacerbation in the group with a decrease (P=0.0021). Furthermore, the cumulative proportion (Kaplan-Meier) of patients who did not suffer exacerbation of CRF was significantly higher in the group in which serum UA/Cr decreased (P=0.0003). CONCLUSIONS: Our data suggest that serum UA may be a useful clinical indicator of CRF exacerbation in patients treated by NPPV.

Two cases of primary pulmonary osteosarcoma.

Two cases of primary pulmonary osteosarcoma are presented. In both cases, chest computed tomography revealed a calcified pulmonary mass and technetium-99m methylene diphosphonate bone scintigraphy showed intense uptake in the pulmonary mass. Primary pulmonary osteosarcoma was suspected on the basis of these radiographic findings. Microscopic examination of tumor specimens obtained by needle biopsy revealed histologic features of osteosarcoma, and this diagnosis was confirmed by postmortem examination of a second specimen in each case. Radiographic and histopathological findings enabled us to diagnose primary pulmonary osteosarcoma, which is one of the rarest types of cancer.

Metastatic renal cell carcinoma presenting as multiple pleural tumours.

A 66-year-old man was admitted with dyspnoea. Chest X-ray and chest computed tomography (CT) demonstrated a left-sided pleural effusion and multiple tumours, suggesting malignant mesothelioma in the left pleural space, but there were no pulmonary lesions. However, abdominal CT revealed a right renal tumour. An ultrasonography-guided needle biopsy of the pleural mass provided evidence of metastatic renal cell carcinoma (RCC). The pleural lesions dramatically decreased in size following right radical nephrectomy and subsequent interferon-alpha treatment. While the thorax is a frequently affected site of RCC, sole pleural metastases are rare and are often secondary to lung involvement. Batson's plexus, a network of vertebral valve-less veins with multiple connections, is likely responsible for the contralateral pleural metastases of RCC.

Clinical features of eleven cases of Mycobacterium avium-intracellulare complex pulmonary disease associated with pneumoconiosis.

The relationship between silicosis and tuberculosis is well known. Also other mycobacteria such as Mycobacterium kansasii often occur in association with pneumoconiosis. However, there are few reports describing an association of M. avium-intracellulare complex (MAC) lung disease and pneumoconiosis. The purpose of the present study is to describe clinical features of MAC respiratory infection associated with pneumoconiosis. Eleven patients with MAC respiratory infection associated with pneumoconiosis (all men, 6 with silicosis and 5 with welders' pneumoconiosis) were collected. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria required by the American Thoracic Society. Radiologically, cavity formation as well as upper lung field predominance of MAC disease were observed in 8 of 11 cases (72.7%). Two of 11 patients died of respiratory failure. Our present study clearly demonstrates that clinical features of MAC respiratory infection associated with pneumoconiosis were different from MAC without underlying diseases.

[A case of quadruple cancer arising in the stomach, lung, liver and prostate].

A 75-year-old man was admitted to our hospital because of severe dyspnea and pollakiuria in October 2001. We diagnosed his illness as carcinomatous pericarditis caused by the recurrence of primary lung cancer and prostatic hypertrophy. He had undergone surgery for gastric cancer in 1986, and for lung cancer in 1996. Furthermore, he had been treated for hepatocellular carcinoma in 1997. He finally died in February 2002 of respiratory failure due to the carcinomatous lymphangitis that followed the lung cancer. After autopsy, a microscopic view of the prostate revealed that he had prostatic carcinoma. Such a case is rare.

Clarithromycin-induced eosinophilic pneumonia.

Clarithromycin (CAM) has been widely used for the treatment of respiratory infection. Macrolides are generally well tolerated and their adverse reactions are rare. An 80-year-old woman with nontuberculous mycobacterium infection was treated with combined chemotherapy, including isoniazid, rifampicin, and ethambutol. She developed a fever and peripheral blood eosinophilia, and new subpleural consolidations were observed on chest radiography three days after add-on therapy with CAM. The symptoms and clinical findings improved with the withdrawal of CAM. Histopathologic examinations confirmed the diagnosis of eosinophilic pneumonia. This is the first report of CAM-induced eosinophilic pneumonia.