Computed tomographic scan of the chest, latex agglutination test and plasma (1AE3)-beta-D-glucan assay in early diagnosis of invasive pulmonary aspergillosis: a prospective study of 215 patients

BACKGROUND AND OBJECTIVES: Blood and radiologic tests are frequently used for diagnosis of invasive pulmonary aspergillosis, but it remains unknown which is more useful for its early diagnosis. Aim of the study was to compare usefulness of computed tomographic (CT) scan of chest, latex agglutination (LA) test and determination of plasma (1-->3)-beta-D-glucan (BDG) levels for early diagnosis of invasive pulmonary aspergillosis (IPA). DESIGN AND METHODS: We treated 215 consecutive patients who underwent cytotoxic chemotherapy. From initiation of chemotherapy until death or discharge, blood samples were taken weekly and subjected to LA and BDG tests. We performed chest CT scans when patients had any signs of pulmonary infection or an antibiotic-resistant fever. RESULTS: Of the 215 patients, 30 (14. 0%) were diagnosed as having IPA. In sixteen cases the diagnosis was definite and in 14 it was suspected. In patient-based analysis, sensitivities of LA and BDG were 44% and 63%, respectively. Sensitivity tended to be lower in patients with IPA localized to the lung than those with disseminated invasive aspergillosis. Specificities were 93% and 74%, respectively. Either a halo or an air-crescent was observed in 7 of the 16 patients with IPA, and all of the IPA patients showed some abnormal signs on chest CT scans. On average, CT scan signs preceded a positive LA test by 7.1 days and a positive BDG assay by 11.5 days. In 6 of the 11 patients who became positive for either LA or BDG assay, CT scan signs preceded the positive results by more than seven days. INTERPRETATION AND CONCLUSIONS: Chest CT scan is more beneficial than the blood tests and X-ray for early diagnosis of IPA.     

Potential Effect of Prolonged Sevoflurane Anesthesia on the Kinetics of [<Superscript>11</Superscript>C]Raclopride in Non-human Primates

Purpose

Positron emission tomography (PET) in non-human primates (NHP) is commonly performed under anesthesia, with sevoflurane being a widely used inhaled anesthetic. PET measurement in NHP can be repeated, and a difference in radioligand kinetics has previously been observed between the first and second PET measurement on the same day using sevoflurane anesthesia. In this study, we evaluated the effect of prolonged sevoflurane anesthesia on kinetics and binding potential (BP_ND) of [¹¹C]raclopride in NHP.

Procedures

Three cynomolgus monkeys underwent two to three PET measurements with [¹¹C]raclopride under continuous sevoflurane anesthesia on the same day. The concentration of sevoflurane was adjusted according to the general conditions and safety parameters of the NHP. Time to peak (TTP) radioactivity in the striatum was estimated from time-activity curves (TACs). The BP_ND in the striatum was calculated by the simplified reference tissue model using the cerebellum as reference region.

Results

In each NHP, the TTP became shorter in the later PET measurements than in the first one. Across all measurements (n = 8), concentration of sevoflurane correlated with TTP (Spearman’s ρ = ? 0.79, p = 0.03), but not with BP_ND (ρ = ? 0.25, p = 0.55).

Conclusions

These data suggest that sevoflurane affects the shape of TACs but has no evident effect on BP_ND in consecutive PET measurements.

     

The linkage among ambulance transports,death and climate parameters in Asahikawa City,Japan

Objective

The aim of this study was to investigate the linkage among climate parameters, total ambulance transports and the number of deaths in Asahikawa City in northern Japan.

Methods

Monthly data on total ambulance transports and the number of deaths from January 2004 to December 2011 were obtained from Asahikawa City Fire Department and the Asahikawa City official website. Climate parameters for the required period were also obtained from the Japan Meteorological Agency, Japan. To adjust for the population, we also used monthly population data on Asahikawa City. The linkage among climate parameters, total ambulance transports and the number of deaths was evaluated by ecological analysis.

Results

The mean air temperature in the Asahikawa area was 7.3 ± 10.1 °C. Total ambulance transports (/a hundred thousand people/day) and the number of deaths (/a hundred thousand people/day) were 10.0 ± 0.6 and 2.6 ± 0.3, respectively. Using quadratic curves, total ambulance transports and the number of deaths were weakly correlated with some climate parameters. The number of deaths was weakly and positively correlated with total ambulance transports.

Conclusion

A weak linkage among climate parameters, total ambulance transports and the number of deaths was noted in Asahikawa City, Japan. However, these associations were not as high as expected.     

Type 1 Autoimmune Pancreatitis Extending along the Main Pancreatic Duct: IgG4-related Pancreatic Periductitis

We herein report a unique form of autoimmune pancreatitis (AIP) spreading along the main pancreatic duct (MPD). A 70-year-old man was referred for a small lesion at the pancreatic neck, accompanying an adjacent cyst and dilated upstream MPD. Four years earlier, health checkup images had shown a pancreatic cyst but no mass lesion. Endoscopic ultrasonography showed a contrast-enhanced, tumorous lesion, mainly occupying the MPD. With a preoperative diagnosis of ductal neoplasms mainly spreading in the MPD, Whipple''s resection was performed. The resected specimens showed MPD periductitis with IgG4-related pathology, indicating type 1 AIP. Clinicians should practice caution concerning the various AIP forms.     

Outcomes in Patients with Classic Hodgkin Lymphoma Treated with ABVD: A Single-center Retrospective Study

Objective Classic Hodgkin lymphoma (CHL) has been regarded as a curable disease when treated appropriately, especially in younger patients, and ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) has been regarded as the standard regimen. However, a relatively poor prognosis has been reported in older patients with CHL, and the efficacy and tolerability of the ABVD regimen has not been fully elucidated. We retrospectively investigated the outcomes in patients with CHL treated with ABVD at our institute. Methods Twenty-five patients were evaluated; 14 were ≤60 years of age, and 11 were >60 years of age (older group). Results The ABVD doses were reduced in all patients in the older group; the median average relative dose intensity was 0.58. In the older group, the 5-year overall survival (OS) and median OS were 100% and not reached, respectively, for patients with early-stage CHL and 66.7% and not reached, respectively, for those with advanced-stage CHL. No patients died of CHL, and only one treatment-related death was observed in the older group. Conclusion ABVD with dose attenuation may represent a feasible and effective strategy for the treatment of older patients with CHL in clinical practice, particularly in those with early-stage disease, although the optimal degree of attenuation remains unclear.     

Angioscopic assessments and clinical outcomes one year after polymer-free biolimus A9-coated coronary stent implantation

BackgroundPolymer-free biolimus A9-coated coronary stent (DCS) has novel features which lead to the expectation of better arterial healing. However, comparisons of intravascular status between DCS and drug-eluting stents (DES), and robust real-word clinical assessments of DCS have been lacking to date.MethodsFrom September 2017 to September 2018, we evaluated the intra-vascular status of 74 DCS implanted in 55 lesions from 43 patients using coronary angioscopy (CAS) approximately one year after implantation from a cohort of 219 lesions in 158 patients. We set 239 second-generation durable-polymer DES (DP-DES) implanted in 211 lesions from 180 patients from a cohort of 2652 lesions in 1914 patients as the control. Angioscopic images were analyzed to determine (1) the dominant degree of neointimal coverage (NIC) over the stent; (2) the heterogeneity of NIC; (3) yellow color grade of the stented segment; and (4) the presence of intra-stent thrombus. The primary outcome was the incidence of thrombus and secondary outcomes were the other CAS findings, and the 1-year clinical outcomes which included target lesion revascularization (TLR) and major adverse cardiac events (MACE). To minimize inter-group differences in baseline characteristics, propensity score matching was performed for clinical outcomes.ResultsIncidence of thrombus adhesion was similar in DCS and DP-DES groups (28.4% versus 22.6%, p = 0.31). However, the dominant NIC grade was significantly higher in DCS (p < 0.001), while NIC was more heterogeneous in DCS than in DP-DES (p = 0.001). Maximum yellow color grade was similar (p = 0.22). After propensity score matching, 202 lesion pairs from 146 patient pairs were retained for analysis. The cumulative incidence of TLR (4.6% versus 3.8%, p = 0.38) and MACE (11.6% versus 11.7%, p = 0.84) was similar for DCS and DP-DES.ConclusionsDCS showed thrombus adhesion and clinical outcomes at 1 year similar to DP-DES. DCS can thus be used with similar safety and efficacy as DP-DES.     

An Irreversible Worsening Cardiac Function after Withdrawing Medical Treatments in a Patient with Dilated Cardiomyopathy: A Pathological Analysis

A 44-year-old man diagnosed with idiopathic dilated cardiomyopathy was admitted to our hospital with acute decompensated heart failure. Seven years before this admission, the first introduction of medication resulted in left ventricular (LV) recovery, which was sustained for several years. However, the patient stopped taking his medication, resulting in worsening of the LV function. Despite the second introduction of medication, the LV function did not improve. We performed cardiac magnetic resonance imaging and an endomyocardial biopsy, which revealed the significant development of cardiac fibrosis that had not been present at the time of the initial diagnosis.     

Anti-myeloma effect of homoharringtonine with concomitant targeting of the myeloma-promoting molecules, Mcl-1, XIAP, and β-catenin

Since a variety of cell intrinsic and extrinsic molecular abnormalities cooperatively promote tumor formation in multiple myeloma (MM), therapeutic approaches that concomitantly target more than one molecule are increasingly attractive. We herein demonstrate the anti-myeloma effect of a cephalotaxus alkaloid, homoharringtonine (HHT), an inhibitor of protein synthesis, through the induction of apoptosis. HHT significantly reduced Mcl-1, a crucial protein involved in myeloma cell survival, in all three myeloma cell lines examined, whereas certain BH3-only proteins, such as Bim, Bik, and Puma, remained unchanged following HHT treatment, and their expression levels depended on the cell type. HHT also reduced the levels of c-FLIP(L/S), activated caspase-8, and induced active truncated-Bid. Thus, HHT-induced apoptosis appears to be mediated via both intrinsic and extrinsic apoptosis pathways, and the resultant imbalance between BH3-only proteins and Mcl-1 may be pivotal for apoptosis by HHT. In addition, HHT treatment resulted in reduced levels of beta-catenin and XIAP proteins, which also contribute to disease progression and resistance to chemotherapy in MM. In combination, HHT enhanced the effects of melphalan, bortezomib, and ABT-737. These results suggest that HHT could constitute an attractive option for MM treatment though its ability to simultaneously target multiple tumor-promoting molecules.     

Circulating interleukin-6 and interleukin-6 receptors in patients with acute and recent myocardial infarction

Interleukin-6 (IL-6), a proinflammatory cytokine, plays a key role in the pathogenesis of coronary artery disease (CAD). We investigated circulating IL-6 and its receptors in patients with CAD. We evaluated 39 Japanese patients with CAD (30 males and 9 females aged 36-79 years), measuring their plasma levels of IL-6 and IL-6 receptors alpha and beta (IL-6R alpha, IL-6R beta). Circulating levels of IL-6, IL-6R alpha and IL-6R beta were measured by an enzyme-linked immunosorbent assay. Blood was sampled immediately after admission and again after 1, 2, 3, 6 and 9 h, then every 12 h for 5 days. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were measured on day 3 after symptom onset. Plasma levels of IL-6 and IL-6Rs were significantly increased in 28 patients with acute myocardial infarction (AMI) compared with 15 normal controls. However, neither IL-6 nor IL-6Rs showed an increase in 6 patients with angina pectoris. We observed two peaks for circulating IL-6 in AMI, the first of which showed a significant correlation with ANP as well as BNP. These results may help to explain why the amount of IL-6 produced is closely related to the severity of myocardial dysfunction in patients with CAD.