Estimation of protein intake using urinary urea nitrogen in patients with liver cirrhosis

Objective. Evaluation of protein intake of patients with liver cirrhosis (LC) would facilitate optimal nutritional support. However, this has never been done based on urinary urea nitrogen (UUN). The aim of this study was to determine the usefulness of the estimated protein intake (EPI) based on UUN in patients with LC. Material and methods. Eighty-two patients with LC were enrolled in this study. The actual protein intake (API) was defined as the dietary protein intake (1.0 g/kg/day) plus supplementation of any enteral diets containing branched-chain amino acids (BCAA). We calculated EPI from UUN using the formula [(UUN (g/day) + 0.031 × body-weight (kg)) ×0.625]. We examined the correlation between EPI and API and the EPI/API ratio (EAR), and the correction based on the results. Results. A significant positive correlation was found between API and EPI (r=0.72, p<0.001). The EAR in all patients was 0.82±0.13. EPI × 1.2 was the correction needed to adjust EAR to 1. The corrected EPI was correlated with API (r=0.704, p<0.001). The corrected EAR of all 82 patients was 0.99±0.16. Conclusions. EPI calculated from UUN is a useful tool for optimal nutritional support in LC patients, and our correction greatly improves EPI accuracy.     

A multicenter clinical study evaluating the confirmed complete molecular response rate in imatinib-treated patients with chronic phase chronic myeloid leukemia by using the international scale of real-time quantitative polymerase chain reaction

Achievement of complete molecular response in patients with chronic phase chronic myeloid leukemia has been recognized as an important milestone in therapy cessation and treatment-free remission; the identification of predictors of complete molecular response in these patients is, therefore, important. This study evaluated complete molecular response rates in imatinib-treated chronic phase chronic myeloid leukemia patients with major molecular response by using the international standardization for quantitative polymerase chain reaction analysis of the breakpoint cluster region-Abelson1 gene. The correlation of complete molecular response with various clinical, pharmacokinetic, and immunological parameters was determined. Complete molecular response was observed in 75/152 patients (49.3%). In the univariate analysis, Sokal score, median time to major molecular response, ABCG2 421C>A, and regulatory T cells were significantly lower in chronic phase chronic myeloid leukemia patients with complete molecular response than in those without complete molecular response. In the multivariate analysis, duration of imatinib treatment (odds ratio: 1.0287, P=0.0003), time to major molecular response from imatinib therapy (odds ratio: 0.9652, P=0.0020), and ABCG2 421C/C genotype (odds ratio: 0.3953, P=0.0284) were independent predictors of complete molecular response. In contrast, number of natural killer cells, BIM deletion polymorphisms, and plasma trough imatinib concentration were not significantly associated with achieving a complete molecular response. Several predictive markers for achieving complete molecular response were identified in this study. According to our findings, some chronic myeloid leukemia patients treated with imatinib may benefit from a switch to second-generation tyrosine kinase inhibitors (ClinicalTrials.gov, UMIN000004935).     

Managing hepatitis B virus carriers with systemic chemotherapy or biologic therapy in the outpatient clinic

Aim: The number of outpatients receiving systemic chemotherapy in Japan has recently increased. We retrospectively examined whether hepatitis B virus (HBV) carriers were safely treated and managed with systemic chemotherapy or biologic agents as outpatients at our oncology center. Methods: A total of 40 115 consecutive infusion chemotherapy or biologic therapies were administrated to 2754 outpatients in the Chemotherapy and Oncology Center at Osaka University Hospital from December 2003 to March 2011. We first studied the prevalence of outpatients with hepatitis B surface antigen (HBsAg), and then retrospectively evaluated a database to determine the frequencies of testing for other HBV‐related markers and the incidence of developing hepatitis or HBV reactivation in patients positive for HBsAg. As a control for comparison, we also examined these same factors in patients with hepatitis C virus antibody (anti‐HCV). Results: The majority of physicians at our hospital screened for HBsAg (95%) and anti‐HCV (94%) prior to administrating chemotherapy. Of the 2754 outpatients, 46 (1.7%) were positive for HBsAg and 90 (3.3%) were positive for anti‐HCV. Fifteen patients that were HBsAg positive were treated with lamivudine or entecavir prior to chemotherapy. None of the patients with HBsAg taking a prophylactic antiviral developed hepatitis, and only one breast cancer patient without prophylactic antiviral treatment (1/31 [3.2%]) developed hepatitis due to HBV reactivation. Conclusion: HBV reactivation occurred in outpatients without prophylactic antiviral treatment, but the incidence was relatively low.     

Monitoring C-reactive protein levels to predict favourable clinical outcomes from tocilizumab treatment in patients with rheumatoid arthritis

Objectives

The inflammatory cytokine interleukin-6 (IL-6) directly stimulates C-reactive protein (CRP) expression. The present study aimed to examine how clinical treatment outcomes of rheumatoid arthritis (RA) with tocilizumab (TCZ), a humanised monoclonal anti-IL-6 receptor antibody, are related to CRP levels monitored for 52 weeks.

Methods

One hundred and twenty-two RA patients who underwent TCZ treatment between May 2008 and September 2009 were registered in the Tsurumai Biologics Communication Registry. Data were collected at initiation of treatment (baseline) and over 52 weeks for Disease Activity Score 28-ESR (DAS28-ESR), Boolean core measurements, serum CRP levels and matrix metalloproteinase-3 levels. To compare clinical results, patients were divided into three groups based on treatment time required to achieve normal CRP levels.

Results

Multivariate analysis using the Cox proportional-hazards regression model found that higher CRP levels at baseline was a significant and independent factor in predicting normal CRP levels over 52 weeks (hazard ratio 0.86 per 1 mg/dL). In contrast, disease duration, concomitant methotrexate use and previous tumour necrosis factor inhibitor failure were not significant factors. Patients with normal CRP levels at 12 weeks of TCZ treatment achieved better clinical outcomes, including remission based on DAS28-ESR criteria, compared to patients with elevated CRP levels at 12 weeks.

Conclusions

Adequate suppression of pathological IL-6 signalling during TCZ treatment improves clinical outcomes and can be monitored with serum CRP levels, a readily available biomarker in clinical practice.     

Synthesis and preliminary evaluation of [18F]FEtP4A,a promising PET tracer for mapping acetylcholinesterase in vivo

N-[18F]Fluoroethyl-4-piperidyl acetate ([18F]FEtP4A), an analog of [11C]MP4A for mapping brain acetylcholineseterase (AchE) activity, was prepared by reacting 4-piperidyl acetate (P4A) with [18F]fluoroethyl bromide ([18F]FEtBr) using a newly developed automated system. Preliminary evaluation showed that the initial uptake of [18F]FEtP4A in the mouse brain was > 8% injected dose/g tissue. The distribution pattern of [18F]FEtP4A in the brain was striatum>cerebral cortex>cerebellum within 10-120 min post-injection, which reflected the distribution rank pattern of AchE activity in the brain. Moreover, chemical analysis of in vivo radioactive metabolites in the mouse brain indicated that 83% of [18F]FEtP4A was hydrolyzed to N-[18F]fluoroethyl-4-piperidinol ([18F]FEtP4OH) after 1 min intravenous injection. From these results, [18F]FEtP4A may become a promising PET tracer for mapping the AchE in vivo.     

Synthesis and evaluation of 3-(4-chlorobenzyl)-8-[11C]methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one: a PET tracer for imaging sigma(1) receptors

3-(4-Chlorobenzyl)-8-methoxy-1,2,3,4-tetrahydrochromeno[3,4-c]pyridin-5-one (1), a putative dopamine D(4) receptor antagonist (k(i) = 8.7 nM), was labeled by positron-emitter (11C) and its pharmacological evaluation was carried out with in vitro quantitative autoradiography and positron emission tomography (PET). 11C-Methylation of a corresponding desmethyl precursor (2) with [11C]CH(3)I gave [11C]1 with >or=98% of radiochemical purity after HPLC purification and 67-90 GBq/micromol of specific activity at the end of synthesis. The in vitro autoradiography using rat brain sections demonstrated that [11C]1 shows no specific binding to the D(4) receptors, but a high specific binding to sigma(1) receptors (IC(50) = 105 nM). In the PET study with monkey brain, [11C]1 was highly taken up by the brain and trapped in the brain for at least 90 min. The distribution pattern of radioactivity in the brain was striatum > thalamus > frontal cortex > cerebellum, which was same as the result of in vitro autoradiography. Pre-treatment with non-radioactive 1 (1 mg/kg) produced a significant reduction of radioactivity in all the regions including the cerebellum. Pre-treatment with (+)pentazocine (1 mg/kg), a selective sigma(1) receptor agonist, also reduced the radioactivity in the same regions to a similar extent. These results indicate that [11C]1 may have some specific binding to the sigma(1) receptors, which is consistent with the result of in vitro autoradiography.     

Length and width of the tendinous portion of the palmaris longus: a cadaver study of adult Japanese

We examined 72 forearms of 36 cadavers to measure the length and width of the tendinous portion of the palmaris longus in adult Japanese. The palmaris longus muscles were absent in both arms in 1 cadaver and in a unilateral arm in 1 cadaver. Double palmaris longus muscles were found in 1 arm in another cadaver. Most cadavers had a typical palmaris longus muscle and tendon shape. The mean length and width of the tendons were 124.6 +/- 17.0 and 4.5 +/- 0.7 mm, respectively, in male specimens and 108.3 +/- 16.4 and 4.0 +/- 0.7 mm in female specimens, respectively. The mean lengths of the forearms were 240.0 +/- 12.6 mm in male specimens and 218.8 +/- 14.6 mm in female specimens. There was a statistically significant correlation between the lengths of the palmaris longus tendon and forearm. These results indicate that one can estimate the length of palmaris longus tendons before surgical intervention.     

Brain MR Findings in Patients with Systemic Lupus Erythematosus with and without Antiphospholipid Antibody Syndrome

BACKGROUND AND PURPOSE:Antiphospholipid syndrome may affect the incidence and pathogenesis of cerebrovascular diseases in patients with systemic lupus erythematosus. We compared the spectrum of MR findings in patients with systemic lupus erythematosus with and without antiphospholipid syndrome.MATERIALS AND METHODS:We identified 256 patients with systemic lupus erythematosus (45 with, 211 without antiphospholipid syndrome) who underwent MR studies; in 145 (57%), we detected abnormalities. These were categorized as large territorial, lacunar, localized cortical, and borderzone infarctions and as microembolisms, basal ganglia lesions, callosal lesions, hemorrhages, and white matter hyperintensity on T2-weighted and/or FLAIR images, and as stenotic arterial lesions on MR angiograms. Logistic regression analysis was performed to compare the MR findings in patients with systemic lupus erythematosus with and without antiphospholipid syndrome, with patient age and antiphospholipid syndrome as the covariates.RESULTS:Abnormal MR findings were more common in patients with systemic lupus erythematosus with antiphospholipid syndrome (73% versus 53%). Large territorial (P = .01), lacunar (P = .01), localized cortical (P < .01), borderzone infarcts (P < .01), basal ganglia lesions (P = .03), stenotic arterial lesions (P = .04), and the rate of positive findings on MR imaging (P = .01) were significantly associated with antiphospholipid syndrome. Irrespective of age, significantly more patients with antiphospholipid syndrome manifested lacunar infarcts in the deep white matter (P < .01), localized cortical infarcts in the territory of the MCA (P < .01), bilateral borderzone infarcts (P < .01), and anterior basal ganglia lesions (P = .01).CONCLUSIONS:Abnormal MR findings were more common in patients with systemic lupus erythematosus with than in those without antiphospholipid syndrome. Large territorial infarctions, lacunar infarctions in the deep white matter, localized cortical infarctions in the MCA territory, bilateral borderzone infarctions, anterior basal ganglia lesions, and stenotic arterial lesions are common MR findings in patients with systemic lupus erythematosus with antiphospholipid syndrome.

Systemic lupus erythematosus (SLE) is an autoimmune disease that frequently manifests with involvement of the central nervous system.^1,2 A previous autopsy study of neuropsychiatric SLE revealed various types of brain lesions including global ischemic changes, parenchymal edema, microhemorrhages, glial hyperplasia, diffuse neuronal/axonal loss, resolved infarction, microthromboemboli, blood vessel remodeling, acute infarction, acute macrohemorrhages, and resolved intracranial hemorrhages.³ A wide spectrum of MR findings in patients with SLE has also been reported.³ SLE is a heterogeneous disease characterized by multisystem autoimmunity, leading to an array of clinical presentations. In addition, there is also a small subset of patients with SLE who show persistently negative antinuclear antibody tests despite having the typical clinical features of SLE. These variabilities can add to the difficulty of timely diagnosis and intervention.⁴ Understanding the wide spectrum of brain pathologic conditions in patients with SLE may help to render an appropriate diagnosis.Antiphospholipid syndrome (APS) is characterized by antiphospholipid antibodies (aPL) and specific thromboembolic phenomena, including deep venous thrombosis and spontaneous abortions.⁵ However, both events are relatively common in the general population and in subjects with autoimmune diseases. Moreover, in patients with thrombosis or spontaneous abortion in whom APS is strongly suspected, conventional aPL are repeatedly negative.⁶ This condition has been called “seronegative APS.”⁷ Therefore, the correct identification of patients with APS can be a complex task. The diagnosis of APS affects treatment options; an antiplatelet and/or anticoagulation therapy is recommended for neuropsychiatric SLE related to aPL, especially for thrombotic cerebrovascular disease.⁸ Therefore, it is important to investigate MR findings in patients with SLE with APS and those without APS. The association of aPL/APS with neurologic involvement has been established,^9,10 but there has been limited reporting of differences in MR findings in patients with SLE with APS and those without APS.¹¹ That study concluded that infarctions and infarcts with white matter hyperintensity (WMH) were more common in patients with SLE with APS, but the study population was relatively small and the specific nature of the MR findings was not described in detail. We characterize the spectrum of MR findings in a large series of patients with SLE and compare our findings in patients with SLE with APS and those without APS.     

Early defects identified by computed tomography angiography are associated with left ventricular dysfunction and exercise intolerance following acute myocardial infarction

Purpose

We evaluated the influence of early defects (EDs) in the infarcted myocardium after reperfusion, detected by computed tomography angiography (CTA), on cardiac function and exercise capacity in the chronic phase.

Materials and methods

We retrospectively analyzed 48 acute myocardial infarction (AMI) patients who underwent both CTA using 64-slice multidetector CT within 14 ± 6 days and cardiopulmonary exercise testing within 3 months after AMI onset between 2005 and 2007. The patients were divided into 2 groups: the EDs <75 % or EDs ≥75 % group. Brain natriuretic peptide (BNP) levels and ejection fraction (EF) were measured 6 months after AMI onset.

Results

The minute ventilation–carbon dioxide production slope was significantly higher in the EDs ≥75 % group (28.7 ± 4.9) than in the EDs <75 % group (25.1 ± 3.1, P = 0.048). EF at 6 months was significantly lower in the EDs ≥75 % group (48.1 ± 12.0 %) than in the EDs <75 % group (56.8 ± 10.0 %, P = 0.01). Log of BNP levels was higher in the EDs ≥75 % group than in the EDs <75 % group (P < 0.001).

Conclusion

EDs detected by CTA in the acute phase of AMI influenced myocardial dysfunction and exercise intolerance in the chronic phase.     

Clinical features,anti-cancer treatments and outcomes of lung cancer patients with combined pulmonary fibrosis and emphysema

Background

Combined pulmonary fibrosis and emphysema (CPFE) patients may be at significantly increased risk of lung cancer compared with either isolated emphysema or pulmonary fibrosis patients. Acute exacerbation (AE) of interstitial lung disease caused by anticancer treatment is the most common lethal complication in Japanese lung cancer patients. Nevertheless, the clinical significance of CPFE compared with isolated idiopathic interstitial pneumonias (IIPs) in patients with lung cancer is not well understood.

Methods

A total of 1536 patients with lung cancer at Nippon Medical School Hospital between March 1998 and October 2011 were retrospectively reviewed. Patients with IIPs were categorized into two groups: (i) CPFE; IIP patients with definite emphysema and (ii) non-CPFE; isolated IIP patients without definite emphysema. The clinical features, anti-cancer treatments and outcomes of the CPFE group were compared with those of the non-CPFE group.

Results

CPFE and isolated IIPs were identified in 88 (5.7%) and 63 (4.1%) patients respectively, with lung cancer. AE associated with initial treatment occurred in 22 (25.0%) patients in the CPFE group and in 8 (12.7%) patients in the non-CPFE group, irrespective of treatment modality. Median overall survival (OS) of the CPFE group was 23.7 months and that of the non-CPFE group was 20.3 months (P = 0.627). Chemotherapy was performed in a total of 83 patients. AE associated with chemotherapy for advanced lung cancer occurred in 6 (13.6%) patients in the CPFE group and 5 (12.8%) patients in the non-CPFE group. Median OS of the CPFE group was 14.9 months and that of the non-CPFE group was 21.6 months (P = 0.679).

Conclusion

CPFE was not an independent risk factor for AE and was not an independent prognosis factor in lung cancer patients with IIPs. Therefore, great care must be exercised with CPFE as well as IIP patients when performing anticancer treatment for patients with lung cancer.