原発性硬化性胆管炎ではcyclooxygenase-2とmicrosomal prostaglandin E synathase-1の発現が亢進し、胆管発がんへの関与が示唆される

Cholangiocarcinoma (CCA) occurs frequently in primary sclerosing cholangitis (PSC). Cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) induced by inflammation are believed to mediate prostaglandin E2 (PGE2) production thereby promoting carcinogenesis. Their expression in PSC-associated CCA tissues and non-neoplastic bile duct epithelial cells (BDECs) in PSC was investigated. COX-2 and mPGES-1 levels in 15 PSC patients (7 with CCA) were scored using immunohistochemical staining. The results were compared with those obtained in CCA tissues and non-neoplastic BDECs (controls) of 15 sporadic CCA patients. Non-neoplastic BDECs from large and small bile ducts were investigated separately. The mRNA expression levels of COX-2 and mPGES-1 in CCA tissues were analyzed by quantitative polymerase chain reaction. Ki-67 immunostaining was performed to evaluate cell proliferation. COX-2 was strongly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC. This expression was significantly upregulated in both compared with sporadic CCA tissues and non-neoplastic BDECs in sporadic CCA (both P<0.01). mPGES-1 was expressed at moderate to strong levels in PSC. Compared with controls, the expression was significantly higher in non-neoplastic small BDECs (P<0.01). COX-2 mRNA levels were significantly higher in PSC-associated tissues than in sporadic CCA tissues (P<0.01). Conversely, no differences were observed in mPGES-1 mRNA levels. Ki-67 labeling indices were higher in PSC-associated CCA tissues and non-neoplastic BDECs in PSC than in controls. In conclusion, COX-2 and mPGES-1 were highly expressed in PSC-associated CCA tissues and non-neoplastic BDECs in PSC, suggesting the involvement of COX-2 and mPGES-1 in cholangiocarcinogenesis.広島大学(Hiroshima University)博士(医学)Philosophy in Medical Sciencedoctora

Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions

The cell-cycle status of hematopoietic stem and progenitor cells (HSPCs) becomes activated following chemotherapy-induced stress, promoting bone marrow (BM) regeneration; however, the underlying molecular mechanism remains elusive. Here we show that BM-resident group 2 innate lymphoid cells (ILC2s) support the recovery of HSPCs from 5-fluorouracil (5-FU)-induced stress by secreting granulocyte-macrophage colony-stimulating factor (GM-CSF). Mechanistically, IL-33 released from chemosensitive B cell progenitors activates MyD88-mediated secretion of GM-CSF in ILC2, suggesting the existence of a B cell-ILC2 axis for maintaining hematopoietic homeostasis. GM-CSF knockout mice treated with 5-FU showed severe loss of myeloid lineage cells, causing lethality, which was rescued by transferring BM ILC2s from wild-type mice. Further, the adoptive transfer of ILC2s to 5-FU-treated mice accelerates hematopoietic recovery, while the reduction of ILC2s results in the opposite effect. Thus, ILC2s may function by "sensing" the damaged BM spaces and subsequently support hematopoietic recovery under stress conditions.Sudo T., Motomura Y., Okuzaki D., et al. Group 2 innate lymphoid cells support hematopoietic recovery under stress conditions. Journal of Experimental Medicine 218, e20200817 (2021); https://doi.org/10.1084/jem.20200817

Risk factors for acute exacerbation following bronchoalveolar lavage in patients with suspected idiopathic pulmonary fibrosis: A retrospective cohort study

Introduction: Bronchoalveolar lavage (BAL) is useful for diagnosing diffuse lung disease and excluding other conditions. However, acute exacerbations (AEs) are recognized as important complications of BAL in patients with idiopathic pulmonary fibrosis (IPF). This study aimed to identify risk factors for BAL-induced AEs in patients with IPF.Material and methods: We retrospectively analyzed the data of 155 patients with suspected IPF who had undergone BAL between January 2013 and December 2018. BAL-related AE was defined as the development of AE within 30 days after the procedure. We compared clinical features and parameters between patients with AE (AE group) and without AE (non-AE group). We also reviewed the relevant reported literature.Results: Among the 155 patients, 5 (3.2%) developed AE within 30 days after BAL. The average duration from BAL to AE onset was 7.8 days (2–16 days). Results from the univariate analysis revealed PaO2 &lt; 75 mm Hg (p = 0.036), neutrophil content in BAL ≥ 7% (p = 0.0061), %DLCO &lt; 50% (p = 0.019), Gender-Age-Physiology (GAP) stage III (p = 0.034), and BAL recovery rates &lt; 30% (p &lt; 0.001) as significant risk factors for post-BAL AE. All five patients who developed AE recovered and were discharged.Conclusions: Disease severity, high neutrophil levels in BAL, and poor BAL recovery rates may be risk factors for BAL-induced AE

Initial Surgical Versus Conservative Strategies in Patients With Asymptomatic Severe Aortic Stenosis

AbstractBackgroundCurrent guidelines generally recommend watchful waiting until symptoms emerge for aortic valve replacement (AVR) in asymptomatic patients with severe aortic stenosis (AS).ObjectivesThe study sought to compare the long-term outcomes of initial AVR versus conservative strategies following the diagnosis of asymptomatic severe AS.MethodsWe used data from a large multicenter registry enrolling 3,815 consecutive patients with severe AS (peak aortic jet velocity >4.0 m/s, or mean aortic pressure gradient >40 mm Hg, or aortic valve area <1.0 cm2) between January 2003 and December 2011. Among 1,808 asymptomatic patients, the initial AVR and conservative strategies were chosen in 291 patients, and 1,517 patients, respectively. Median follow-up was 1,361 days with 90% follow-up rate at 2 years. The propensity score–matched cohort of 582 patients (n = 291 in each group) was developed as the main analysis set for the current report.ResultsBaseline characteristics of the propensity score–matched cohort were largely comparable, except for the slightly younger age and the greater AS severity in the initial AVR group. In the conservative group, AVR was performed in 41% of patients during follow-up. The cumulative 5-year incidences of all-cause death and heart failure hospitalization were significantly lower in the initial AVR group than in the conservative group (15.4% vs. 26.4%, p = 0.009; 3.8% vs. 19.9%, p < 0.001, respectively).ConclusionsThe long-term outcome of asymptomatic patients with severe AS was dismal when managed conservatively in this real-world analysis and might be substantially improved by an initial AVR strategy. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140

Preoperative Biliary Drainage in Cases of Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Chemotherapy and Surgery

Objective. To elucidate the optimum preoperative biliary drainage method for patients with pancreatic cancer treated with neoadjuvant chemotherapy (NAC). Material and Methods. From January 2010 through December 2014, 20 patients with borderline resectable pancreatic cancer underwent preoperative biliary drainage and NAC with a plastic or metallic stent and received NAC at Hiroshima University Hospital. We retrospectively analyzed delayed NAC and complication rates due to biliary drainage, effect of stent type on perioperative factors, and hospitalization costs from diagnosis to surgery. Results. There were 11 cases of preoperative biliary drainage with plastic stents and nine metallic stents. The median age was 64.5 years; delayed NAC occurred in 9 cases with plastic stent and 1 case with metallic stent (p=0.01). The complication rates due to biliary drainage were 0% (0/9) with metallic stents and 72.7% (8/11) with plastic stents (p=0.01). Cumulative rates of complications determined with the Kaplan-Meier method on day 90 were 60% with plastic stents and 0% with metallic stents (log-rank test, p=0.012). There were no significant differences between group in perioperative factors or hospitalization costs from diagnosis to surgery. Conclusions. Metallic stent implantation may be effective for preoperative biliary drainage for pancreatic cancer treated with NAC

Transabdominal Ultrasound Real-time Tissue Elastography as a Screening Method for Early Chronic Pancreatitis

Background and Purpose: The concept of early chronic pancreatitis was proposed in Japan with the aim to improve the prognosis of patients with chronic pancreatitis. Endoscopic ultrasonography plays an important role in early diagnoses, but is limited by its invasiveness and poor objectivity. Hence, this study aimed to determine the usefulness of transabdominal ultrasound real-time tissue elastography as a screening method for early chronic pancreatitis. Methods: We retrospectively examined 73 patients who underwent simultaneous ultrasound real-time tissue elastography and endoscopic ultrasonography from 2011 to 2014. The correlation between feature values (MEAN, %AREA, COMP) calculated by real-time tissue elastography and the Rosemont classification of endoscopic ultrasonography diagnostic criteria for chronic pancreatitis, and the diagnostic ability of ultrasound real-time tissue elastography to recognize “indeterminate for chronic pancreatitis” findings, which correspond to early chronic pancreatitis, were evaluated. Main Results: Based on the Rosemont classification, 26 patients were “normal”, 16 were “indeterminate for chronic pancreatitis”, 13 were “suggestive of chronic pancreatitis”, and 18 were “consistent with chronic ancreatitis”. There were significant correlations between the feature values (MEAN, %AREA, COMP) and the Rosemont classification (p < 0.001; ρ = –0.788, 0.779, and 0.489, respectively). The area under the curve for the ability of MEAN to diagnose “indeterminate for chronic pancreatitis” was 0.889 (sensitivity, 93.8%; specificity, 76.9%). Conclusions: The feature values calculated by ultrasound real-time tissue elastography were correlated with the Rosemont classification. Ultrasound real-time tissue elastography may be a useful screening method for early chronic pancreatitis

Ischemic Stroke in Acute Decompensated Heart Failure: From the KCHF Registry

[Background] Heart failure (HF) is a known risk factor for ischemic stroke, but data regarding ischemic stroke during hospitalization for acute decompensated HF (ADHF) are limited. [Methods and Results] We analyzed the data from a multicenter registry (Kyoto Congestive Heart Failure [KCHF] Registry) that enrolled 4056 consecutive patients with ADHF in Japan (mean age, 78 years; men, 2238 patients [55%]; acute coronary syndrome [ACS], 239 patients [5.9%]). We investigated the incidence and predictors of ischemic stroke during hospitalization for ADHF. During the hospitalization, 63 patients (1.6%) developed ischemic stroke. The median interval from admission to the onset of ischemic stroke was 7 [interquartile range: 2–14] days, and the most common underlying cause was cardioembolism (64%). Men (OR, 1.87; 95%CI, 1.11–3.24), ACS (OR, 2.31; 95%CI, 1.01–4.93), absence of prior HF hospitalization (OR, 2.21; 95%CI, 1.24–4.21), and high B‐type natriuretic peptide (BNP)/N‐terminal proBNP (NT‐proBNP) levels (above the median) at admission (OR, 3.15; 95%CI, 1.84–5.60) were independently associated with ischemic stroke. In patients without ACS, the independent risk factors for ischemic stroke were fully consistent with those in the main analysis. Higher quartiles of BNP/NT‐proBNP levels were significantly associated with higher incidence of ischemic stroke (P for trend, <0.001). Patients with ischemic stroke showed higher in‐hospital mortality, longer length of hospital stay, and poorer functional status at discharge. [Conclusions] During hospitalization for ADHF, 1.6% of the patients developed ischemic stroke. Men, ACS, absence of prior HF hospitalization, and high BNP/NT‐proBNP levels at admission were independently associated with ischemic stroke

Missing western half of the Pacific Plate: Geochemical nature of the Izanagi-Pacific Ridge interaction with a stationary boundary between the Indian and Pacific mantles

The source mantle of the basaltic ocean crust on the western half of the Pacific Plate was examined using Pb–Nd–Hf isotopes. The results showed that the subducted Izanagi–Pacific Ridge (IPR) formed from both Pacific (180–∼80 Ma) and Indian (∼80–70 Ma) mantles. The western Pacific Plate becomes younger westward and is thought to have formed from the IPR. The ridge was subducted along the Kurile–Japan–Nankai–Ryukyu (KJNR) Trench at 60–55 Ma and leading edge of the Pacific Plate is currently stagnated in the mantle transition zone. Conversely, the entire eastern half of the Pacific Plate, formed from isotopically distinct Pacific mantle along the East Pacific Rise and the Juan de Fuca Ridge, largely remains on the seafloor. The subducted IPR is inaccessible; therefore, questions regarding which mantle might be responsible for the formation of the western half of the Pacific Plate remain controversial. Knowing the source of the IPR basalts provides insight into the Indian–Pacific mantle boundary before the Cenozoic. Isotopic compositions of the basalts from borehole cores (165–130 Ma) in the western Pacific show that the surface oceanic crust is of Pacific mantle origin. However, the accreted ocean floor basalts (∼80–70 Ma) in the accretionary prism along the KJNR Trench have Indian mantle signatures. This indicates the younger western Pacific Plate of IPR origin formed partly from Indian mantle and that the Indian–Pacific mantle boundary has been stationary in the western Pacific at least since the Cretaceous