Exertional evaluation for BT

Bronchial thermoplasty (BT) had been reported to improve the symptoms of severe asthma. However, the exertional responses of BT based on the mechanisms have not been elucidated. A 57-year-old man and a 60-year-old woman underwent BT due to intractable severe asthma. We evaluated the therapeutic effects of BT using cardiopulmonary exercise testing (CPET). After BT, the exercise time during CPET substantially prolonged reducing exertional dyspnea in the former (good), but not in the latter (poor). In the good responder, the high air remaining in the lung after expiration (i.e., inspiratory tidal volume minus expiratory tidal volume) during CPET decreased after BT. In contrast, in the poor responder, the high air remaining after expiration during exercise was not obtained before BT. Further investigations are necessary to confirm that the presence or absence of the exertional wasted ventilation on CPET may be informative to evaluate the therapeutic effects of BT

The relationship between the PD-L1 expression of surgically resected and fine-needle aspiration specimens for patients with pancreatic cancer

BACKGROUND: Recently, therapeutic antibodies against programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) have shown promising clinical results for several solid tumors, including pancreatic cancer. In this study, we evaluated the relationship between the PD-L1 expression of surgical resected and fine-needle aspiration (FNA) specimens for patients with pancreatic cancer. METHODS: Of 121 patients who underwent endoscopic ultrasound-guided (EUS)-FNA before surgery for pancreatic cancer in an academic center, the 94 (78%) with adequate FNA specimens for a histological evaluation were retrospectively analyzed. All the patients had undergone upfront surgery without any chemotherapy or radiotherapy. We performed immunohistochemistry (IHC) staining to investigate the PD-L1 expression in both resected and FNA specimens. The positive-stained cells were counted, and their percentage was used for the investigation. RESULTS: Of the 94 patients, 16 (17%) and 11 (10%) were defined as positive on resected cancer specimens using cutoff points of 5% and 10% positively stained cancer cell counts, respectively. The concordance rates for the positive frequency of PD-L1 expression between resected and FNA specimens were 44% (7/16) and 55% (6/11) when the positivity was set to ≥ 5% and ≥ 10%, respectively. The concordance rates for the negative frequency of PD-L1 expression between two specimens were 97% (76/78) and 99% (82/83) when the positivity was set to ≥ 5% and ≥ 10%, respectively. CONCLUSIONS: Approximately, half of the patients with PD-L1 expression positive and almost all the patients with PD-L1 expression negative could be diagnosed on FNA specimens

Iron deposition in autopsied liver on patients receiving long-term TPN

Background Vitamins and minerals are routinely administered by total parenteral nutrition (TPN). However, in Japan, adjustments in iron dosage are difficult because blended mineral preparations are often used. It is therefore unclear whether the iron content is appropriate in cases of long-term TPN. The aim of the study was to assess the influence of iron administration by long-term TPN on iron deposition in post-mortem liver samples isolated from older deceased patients. Methods Liver tissues were collected from post-mortem autopsies of 187 patients over a period of 15 years. Samples were stained with Prussian blue and histologically evaluated from Grade 0–V by at least three different observers. Specimens with positive and negative iron staining were compared, and positive samples were grouped according to the level and distribution of the staining. Post-mortem blood obtained from the subclavian vein during autopsy was also analysed. Samples were collected for the measurement of unsaturated serum iron, serum iron, albumin, prealbumin, hepcidin, and IL-6 concentrations. Results Iron accumulation in the liver was significantly higher in male patients (p = 0.005) with a history of surgery (p = 0.044) or central vein administration of iron (p<0.001). Additionally, the duration of TPN in the iron-positive group was significantly longer than in the iron-negative group (p = 0.038). Serum analysis revealed that unsaturated serum iron was significantly higher in the iron-negative group and that ferritin and serum iron were significantly higher in the iron-positive group. No other statistically significant differences were observed between the two groups. Conclusions Chronic intravenous administration of iron was associated with iron deposition in the liver, even when given the minimum recommended dosage. In long-term TPN patients, the iron dose should therefore be carefully considered

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Linear chain aldehydes evoke calcium responses in B16 melanoma cells

Oxidative stress is involved in various physiological impairing stages, such as aging, diabetes, atherosclerosis, cirrhosis, and neurological disorders. Recent research indicates that aldehyde compounds derived from oxidized lipids increase in cancer patients compared to healthy individuals. Among of them, hexanal, a six-carbon liner chain aldehyde, is commonly found in cancer patients. Lipid oxidation products including aldehydes are in general chemically unstable and react with biological molecules such as proteins. The purpose of this study is to investigate effects of lipid-derived aldehydes and the related compounds on intracellular Ca2+ responses in B16 melanoma cells. Hexanal-induced [Ca2+]i elevation is observed in B16 cells in a dose dependent manner, but [Ca2+]i changes were observed neither in 3T3-L1 cells nor Caco-2 cells. Propanal, a chain length analogue of hexanal, elicited no change in [Ca2+]i, but nonanal initiated [Ca2+]i increases. Analogue compounds of hexanal failed to induce [Ca2+]i elevation. Furthermore, unsaturated aldehydes known as TRPA1 channel agonists also failed to alter [Ca2+]i levels in B16 melanoma cells. Pharmacological spectra using inhibitors against intracellular Ca2+ signaling suggest that hexanal-induced [Ca2+]i responses in B16 cells might be involved in TRP channels other than TRPA1. Our results suggest that saturated aliphatic chain aldehydes would be novel compounds for initiating [Ca2+]i increases through very strict recognitions of chain saturation, aldehydic base structures, and chain lengths in B16 melanoma cells. B16 cells would have sensing mechanisms for oxidative status and/or metabolic activities in their growth environment

Clinical, Laboratory, and Imaging Characteristics of Transient Ischemic Attack Caused by Large Artery Lesions: A Comparison between Carotid and Intracranial Arteries

Background/Aims: The aims of this study were to determine the differences in clinical characteristics and the risk of ischemic stroke between patients with transient ischemic attack (TIA) attributable to extracranial carotid and intracranial artery occlusive lesions. Methods: Among 445 patients admitted to our stroke care unit within 48 h of TIA onset between April 2008 and December 2013, 85 patients (63 men, mean age 69.4 years) with large artery occlusive lesions relevant to symptoms were included in this study. The primary endpoints were ischemic stroke at 2 and 90 days after TIA onset. Results: Twenty-eight patients had carotid artery occlusive lesions (extracranial group), and 57 patients had intracranial artery occlusive lesions (intracranial group). Patients in the intracranial group were significantly younger, had lower levels of fibrinogen, and were less likely to have occlusion when compared with those in the extracranial group. Eleven patients in the extracranial group and none in the intracranial group underwent revascularization procedures within 90 days of TIA onset. The 2-day risk (14.2 vs. 0%, p = 0.044) and the 90-day risk (17.1 vs. 0%, p = 0.020) of ischemic stroke after TIA onset were significantly higher in the intracranial group than in the extracranial group. Conclusions: Among our patients with TIA caused by large artery disease, patients with intracranial artery occlusive lesions were more frequent and were at higher risk of early ischemic stroke than those with extracranial carotid artery occlusive lesions. These data highlight the importance of prompt assessment of intracranial artery lesions in patients with TIA

Diagnostic Utility of the PD-L1 Immunostaining in Biopsy Specimens of Patients with Biliary Tract Neoplasms

Background　Anti-programmed death 1/programmed death ligand 1 (PD1/PD-L1) antibodies have been successfully used as treatment agents for several solid tumors; however, it is difficult to predict their effectiveness. We evaluated whether biopsy specimens could predict the positive status of PD-L1 in surgically resected tissue. Methods　Among 91 patients who underwent tissue sampling with endoscopic or liver biopsy before surgery for biliary tract neoplasms in an academic center, 45 (49%) patients were selected for retrospective analysis because the quality and quantity of their biopsy specimens were adequate for histologic evaluation. We performed immunohistochemical staining to investigate the PD-L1 expression in both resected and biopsy specimens. The percentage of the positively stained cells was calculated for subsequent use in the correlation investigation. Results　The biopsy methods were endoscopic retrograde cholangiopancreatography (ERCP) in 28 cases, percutaneous liver biopsy in 10 cases, and endoscopic ultrasound fine-needle aspiration in 7 cases. Among the 45 patients, when patients with > 10% positive tumor cells in surgically resected tissues were regarded as truly positive PD-L1, the positive and negative concordance rates between surgically resected tissues and biopsy samples were 56% (5/9) and 100% (36/36), respectively. With regard to the use of preoperative biopsy as a diagnostic tool, all (5/5) PD-L1-positive patients had a positive resected specimen. The accuracy of each biopsy method was as follows: ERCP, 89% (25/28); fine-needle aspiration, 86% (6/7); and liver biopsy, 100% (10/10). Conclusions　Biopsy samples could be a surrogate material for the assessment of the PD-L1 expression with substantial positive and high negative concordance rates