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The dye injection method has been applied to many species to analyze the xylem water transport pathway in trees. However, traditional dye injection methods introduced dye tracers from the surface of cut stems, including several annual rings. Furthermore, the traditional dye injection method did not evaluate radial water movement from the outermost annual rings to the inner annual rings. In this study, we assessed the difference in radial water movement visualized by an injected dye, between stem base cut and current-year root cut samples of Salix gracilistyla Miq., with current-year roots grown hydroponically. The results showed that the number of stained annual rings in the root cut samples was smaller than that in the stem cut samples, and the percentage of stained vessels in the root cut samples was significantly smaller than that in the stem base cut samples in the second and third annual rings. In the current-year root cut samples, water transport mainly occurred in the outermost rings from the current-year roots to leaves. In addition, the theoretical hydraulic conductivity of stained vessels in the stem cut samples was higher in the current-year root cut samples in the second and third annual rings. These findings indicate that the previously reported dye injection method using stem cut samples overestimated the water transport pathway in the inner part of the stems. Moreover, previous hydraulic conductivity measurement methods might not have considered the effects of radial resistance through the annual ring boundary, and they might have overestimated the hydraulic conductivity in the inner annual rings.

Cell walls, especially secondary cell walls (SCWs), maintain cell shape and reinforce wood, but their structure and shape can be altered in response to gravity. In hardwood trees, tension wood is formed along the upper side of a bending stem and contains wood fiber cells that have a gelatinous layer (G-layer) inside the SCW. In a previous study, we generated nst/snd quadruple-knockout aspens (Populus tremula × Populus tremuloides), in which SCW formation was impaired in 99% of the wood fiber cells. In the present study, we produced nst/snd triple-knockout aspens, in which a large number of wood fibers had thinner SCWs than the wild type (WT) and some had no SCW. Because SCW layers are always formed prior to G-layer deposition, the nst/snd mutants raise interesting questions of whether the mutants can form G-layers without SCW and whether they can control their postures in response to changes in gravitational direction. The nst/snd mutants and the WT plants showed growth eccentricity and vessel frequency reduction when grown on an incline, but the triple mutants recovered their upright growth only slightly, and the quadruple mutants were unable to maintain their postures. The mutants clearly showed that the G-layers were formed in SCW-containing wood fibers but not in those lacking the SCW. Our results indicate that SCWs are essential for G-layer formation and posture control. Furthermore, each wood fiber cell may be able to recognize its cell wall developmental stage to initiate the formation of the G-layer as a response to gravistimulation.

Background The use of baseline tumor burden (TB) as a prognostic factor for non‐small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) and associations between TB and other prognostic biomarkers remain unclear. In this study, we investigated the association between TB and survival in NSCLC patients treated with ICIs in comparison with other biomarkers. Methods We retrospectively evaluated 83 NSCLC patients with ICIs administered between February 2016 and December 2018. TB was measured as the sum of the unidimensional diameters of up to five target lesions. Results The median observation period was 14.2 months. A total of 42 patients died during the follow‐up. Univariate Cox regression analysis showed that baseline TB was associated with OS. Cox regression analysis adjusted for Eastern Cooperative Oncology Group performance status (ECOG PS) alone or with addition of programmed cell death ligand 1 expression and treatment line showed that TB was a prognostic factor for OS. Using time‐dependent receiver operating characteristic curve analysis, the optimal TB cutoff for predicting OS was 12 cm, and patients were divided into a high TB group (n = 21) and a low TB group (n = 62). The low TB group achieved significantly longer OS than the high TB group (median OS: 18.5 months, [95% CI = 11.7‐not reached] vs. 2.3 months [95% CI = 1.3–2.9], P

Objective To clarify the incidence, risk factors, and impact of malignancy in patients with PM/DM-associated interstitial lung disease (ILD). Methods This study used data from 497 patients with PM/DM-associated ILD enrolled in a multicentre, retrospective and prospective cohort of incident cases. Cancer-associated myositis (CAM) was defined as malignancy diagnosed within 3 years before or after PM/DM diagnosis. Demographic and clinical information was recorded at the time of diagnosis, and data about the occurrence of mortality and malignancy was collected. Results CAM was identified in 32 patients with PM/DM-associated ILD (6.4%). Patients with CAM were older (64 vs 55 years, P < 0.001), presented with arthritis less frequently (24% vs 49%, P = 0.01), and showed a lower level of serum Krebs von den Lungen-6 (687 vs 820 IU/l, P = 0.03) than those without CAM. The distribution of myositis-specific autoantibodies, including anti-melanoma differentiation–associated gene 5, anti-aminoacyl tRNA synthetase, and anti-transcriptional intermediary factor 1-γ antibodies, did not differ between the groups. Survival analysis demonstrated that CAM patients had a poorer survival than non-CAM patients (P = 0.006), primarily due to excess deaths by concomitant malignancy, while mortality due to ILD-related respiratory failure was similar between the groups (P = 0.51). Conclusion Concomitant malignancy can occur in patients with PM/DM-associated ILD, and has significant impact on mortality. Older age, lack of arthritis, and a lower level of serum Krebs von den Lungen-6 at diagnosis are predictors of concomitant malignancy.

Tree age derived from annual-ring counts provides fundamental information on forest stands and individual trees in temperate forests. However, discontinuous growth in the trunk may cause inaccuracies in annual-ring counts, and the effect of radial growth rate and interspecific differences on discontinuous ring formation have not been evaluated in the same forest stand. We investigated the occurrence of discontinuous rings at the base of 435 tree trunk disks of 16 evergreen and 15 deciduous hardwood tree species growing in a temperate forest of Japan. The effects of tree age and radial growth rate on frequency of discontinuous rings and their interspecific differences were evaluated by a generalized linear mixed-effect model. Discontinuous rings were observed in 29 of the 31 species in 330 individuals, which is about 75% of the total number of individuals examined. The number of discontinuous rings proportionally decreased with the growth rate and increased with the tree age. On the other hand, the effects of the growth rate were different among species. The majority of species at the study site contained frequent discontinuous rings in the trunk base. Annual-ring counts from a single core would lead to underestimation of tree ages in this case. Stem disks or increment cores taken in multiple directions at ground level would be useful for accurate estimation of tree age in temperate hardwood forests.

We assessed the narrow-sense heredity and genetic gains of multiple traits obtained using the indirect selection method for progeny of Cryptomeria japonica D. Don by artificial crossing. Using stress wave velocity and Pilodyn penetration depth as indicative parameters, wood properties could be improved in future generations of C. japonica plus trees and forest breeding programs will become more efficient. To advance generations of C. japonica D. Don breeding populations, the narrow-sense heredity and genetic gain of traits of progenies are required to assess the practical genetic performance of parental trees and improve traits. We assessed the genetic gains in both growth characteristics and wood properties by indirect selection using full-sib progenies of C. japonica plus trees produced through artificial crosses. In 18-year-old progenies of 549 trees, we assessed growth characteristics, dynamic modulus of elasticity, basic density, stress wave velocity, and Pilodyn penetration depth. Genetic parameters were calculated using a mixed model and the breedR package. The genetic correlation between growth characteristics and wood properties was low. The efficiencies of indirect selection for dynamic modulus of elasticity by stress wave velocity and for basic densities by Pilodyn penetration depth were higher than those for growth characteristics by stress wave velocity and Pilodyn penetration depth, respectively. Strong correlations were found between the parental clonal values and breeding values of parental trees predicted from progeny using stress wave velocity and Pilodyn penetration depth. Using stress wave velocity and Pilodyn penetration depth as indicative parameters, future generations of C. japonica plus trees could produce superior wood properties. Growth characteristics and wood properties are independent; thus, both traits could be genetically improved compatibly.

Rawanbuki, a variety of Japanese butterbur (Petasites japonicus subsp. giganteus), grow naturally along the Rawan River, Hokkaido, northern Japan. Most plants reach 2–3 m in height and 10 cm in diameter in 2 months and are much larger than those grown along other rivers. We examined the hypothesis that nutrients exported from upland streams enhance the growth of the Rawanbuki. Nutrient concentrations, including nitrogen, phosphorus, and base cations, in the Rawan River were much higher than those in rivers of adjacent watersheds. High nutrient concentrations and moisture contents were found in soil along the Rawan River and a significant relationship was found between physicochemical soil conditions and aboveground biomass of butterburs. This indicates that extremely large Rawanbuki plants could be caused by these high nutrient concentrations and moisture contents in the soils. A manipulation experiment showed that fertilization simulated the growth environment along the Rawan River and enhanced the stem height and stem diameter of butterburs. This study concluded that the extremely large butterburs are caused by a large amount of nutrients exported from upland areas. These results are the first demonstration of the role of stream water nutrients in enlarging agricultural crops.

Valsiner, Sato, and colleagues have created new methodological materials for cultural psychology in the last 17 years, which are called the Trajectory Equifinality Approach (TEA). TEA is a triarchic system that consists of three subcomponents, namely, the Historically Structured Inviting (HSI), the Trajectory Equifinality Modeling (TEM), and the Three Layers Model of Genesis (TLMG). This chapter explores the meeting between Valsiner and Sato and examines how serendipity created the TEA. The process of turning chance into destiny involved the obligatory passage point of inviting Valsiner, as a visiting professor, to the Ritsumeikan University in 2004 and the enthusiasm of Japanese researchers who tried to decipher his ideas. After explaining the three subcomponents of TEA (i.e., HSI, TEM, and TLMG), this goes a step further to examine how TEA is developing not only in Japan but also in Brazil and other countries.

ANCA-associated RPGN leads to renal failure through systemic vasculitis and diffuse crescentic glomerulonephritis. MPO-ANCA-RPGN patients are highly susceptible to infections. Our aim in this study was to uncover reasons why these patients were susceptible to infections. We analyzed various aspects of type I interferon system including HVJ-stimulated IFN-α producing capacity and plasmacytoid dendritic cell (pDC) number in whole blood in MPO-ANCA-RPGN patients. Compared with healthy subjects, MPO-ANCA-RPGN patients showed impaired HVJ-stimulated IFN-α producing capacity and lower pDC number with or without glucocorticoid treatment. Immuno-histological staining of MPO-ANCA-RPGN kidney samples revealed a few but apparent pDC in T cell infiltrating regions even in patients with low pDC number in their peripheral blood. Patients' low HVJ-stimulated IFN-α producing capacity and pDC numbers persisted even after patients underwent several years of treatment. Former infection was determined using patients' serum BPI, Lamp-2 and Calprotectin, since they are reflective of a history of infection. These markers were higher in MPO-ANCA-RPGN patients than in healthy subjects. These results indicate that impaired HVJ-stimulated IFN-α production as well as dysfunction of the IFN system might have resulted from a previous bout of infection and can be partially implicated in patients' long-term susceptibility and vulnerability to infection.

Recent studies have suggested that an increased peripheral monocyte count predicts a poor outcome in fibrosing interstitial lung disease (ILD). However, the association between an increased monocyte count and acute exacerbations (AEs) of fibrosing ILD remains to be elucidated. Our retrospective cohort study aimed to assess the impact of peripheral monocyte count on AEs of fibrosing ILD. We analyzed the electronic medical records of 122 consecutive patients with fibrosing ILD and no prior history of an AE, who were treated with anti-fibrotic agents from August 2015 to December 2018. We determined their peripheral monocyte counts at anti-fibrotic agent initiation and performed univariate and multivariate Cox regression analyses of time-to-first AE after anti-fibrotic agent initiation to assess the impact of monocyte count on AEs of fibrosing ILD. Twenty-six patients developed an AE during the follow-up period, and there was an increased monocyte count at anti-fibrotic agent initiation in these patients compared to those who did not develop an AE. There was also a significantly shorter time-to-first AE of fibrosing ILD in patients with a higher absolute monocyte count. Subgroup analyses indicated similar results regardless of the idiopathic pulmonary fibrosis diagnoses. This association was independently significant after adjusting for the severity of the fibrosing ILD. Using our results, we developed a simple scoring system consisting of two factors—monocyte count (<>380 µL−1) and ILD-gender, age, physiology score (<>4 points). Our findings suggest that the absolute monocyte count is an independent significant risk factor for AE in patients with fibrosing ILD. Our simple scoring system may be a predictor for AEs of fibrosing ILD, although further studies are needed to verify our findings.

The suppression of apical growth and radial trunk growth in trees under shade is a key factor in the competition mechanism among individuals in natural and artificial forests. However, the timing of apical and radial growth suppression after shading and the physiological processes involved have not been evaluated precisely. Twenty-one Abies sachalinensis seedlings of 5-years-old were shaded artificially under a relative light intensity of 5% for 70 days from August 1, and the histological changes of the terminal bud and terminally lateral bud of terminal leader and the cambial zone of the trunk base were analyzed periodically. In shade-grown trees, cell death of the leaf primordia in a terminal bud of terminal leader was observed in one of the three samples after 56 and 70 days of shading, whereas the leaf primordia in a terminal bud of terminal leader in all open-grown trees survived until the end of the experiment. In addition, the leaf primordia of the terminally lateral buds of terminal leader retained their cell nuclei until the end of the experiment. No histological changes were observed in the cambial cells after shading, but the shade-grown trees had less cambial activity than the open-grown trees through the experiment. Strong shading appeared to inhibit the formation and survival of cells in the terminal bud of terminal leader rather than the terminally lateral buds of terminal leader and the cambium. The suppression of the terminal bud growth and elongation of the surviving lateral buds would result in an umbrella-shaped crown under shade.

Objectives The use of immune checkpoint inhibitors (ICIs) for advanced non-small cell lung cancer (NSCLC) has demonstrated survival benefits, although some treatment responders (defined as patients with non-progressive disease) are forced to discontinue treatment because of severe immune-related adverse events (irAEs). An association between treatment efficacy and irAEs has been reported. However, it is unclear which treatment responders are likely to develop severe irAEs. We aimed to examine risk factors for ICI-related severe irAEs in patients with NSCLC. Materials and methods Between February 2016 and October 2018, we retrospectively evaluated 42 patients with NSCLC at our institution who responded to ICI treatment. Tumor burden was measured as the sum of the unidimensional diameters of up to five target lesions, according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results ICIs were discontinued in 15 of 42 treatment responders because of severe irAEs. Tumor burden was a significant independent predictor of severe irAEs (p = 0.03). The odds ratio of severe irAEs and tumor burden over 90 mm was 8.62 (95% confidence interval = 1.96–37.9, p = 0.004). Conclusion A high tumor burden was a risk factor for severe irAEs in patients with NSCLC who responded to ICI treatment.

Background and objective Here, we present real-world data on the incidence and risk factors of acute exacerbation (AE) in patients with chronic fibrotic interstitial pneumonia (CFIP) treated with antifibrotic agents, which has been previously poorly documented. Methods We retrospectively examined clinical characteristics, incidence and risk factors of AE in a cohort of 100 patients with CFIP (n = 75, idiopathic pulmonary fibrosis [IPF]; n = 25, other conditions), all of whom received antifibrotic agents in a real-world setting. Results The median follow-up was 17.4 months (interquartile range [IQR], 6.6 to 26.7 months). During the follow-up periods, 21 patients experienced AE after starting antifibrotic agents. The estimated 1-, 2-, and 3-year AE incidence rates were 11.4% (95% confidence interval [95%CI], 6.2–20.3%), 32% (95%CI, 20.7–47.4%), and 36.3% (95%CI 23.5–53.1%), respectively. Decreased baseline lung function (forced vital capacity and carbon monoxide diffusing capacity of the lung), existence of pulmonary hypertension estimated from an echocardiogram, higher Interstitial Lung Disease-Gender, Age, and Physiology (ILD-GAP) score, supplementary oxygen, and concomitant corticosteroid and proton-pump inhibitor (PPI) use upon starting the antifibrotic agent were risk factors of AE. Concomitant corticosteroid and PPI use and corticosteroid dose were risk factor of AE in a multivariate Cox regression hazard model adjusting for ILD-GAP score. Conclusion AE of CFIP is more common in patients with physiologically and functionally advanced disease under antifibrotic agents. Prudent use of corticosteroids and PPIs when initiating antifibrotic agents may be recommended. Further studies are warranted. Electronic supplementary material The online version of this article (10.1186/s12890-019-0880-0) contains supplementary material, which is available to authorized users.

In a road bridge, drainage facilities are installed to discharge the water on the bridge surface. For each drainage facility, installation spacings are exemplified by waterproof manuals and others, but the quantitative sharing and drainage capacity of each facility and bridge surface have not been clarified. Also, it is thought that water will be stagnant due to bridge surface irregularities generated during construction or during service. However, no regulations on the concavities and convexities about the slab surface are clearly shown in construction standards. Therefore, in this study, surface shape measurement and water sprinkling test on unpaved actual bridge slab were carried out. From the results, we confirmed the possibility that irregularities on the slab surface affect the tendency of local water stagnation. Since only one bridge was studied in the current study, we have not confirmed the influence of gradient magnitude on the drainage capacity of uneven slab surface. It is a future task to clarify the relation between surface gradient and allowable irregularity size and to develop a standard for controlling irregularities on slab and pavement surface.

Although previous studies have suggested that branch dieback and whole-plant death due to drought stress occur at 50-88% loss of stem hydraulic conductivity (P50 and P88, respectively), the dynamics of catastrophic failure in the water-conducting pathways in whole plants subjected to drought remain poorly understood. We examined the dynamics of drought stress tolerance in 3-year-old Japanese black pine (Pinus thunbergii Parl.). We nondestructively monitored (i) the spatial distribution of drought-induced embolisms in the stem at greater than P50 and (ii) recovery from embolisms following rehydration. Stem water distributions were visualized by cryo-scanning electron microscopy. The percentages of both embolized area and loss of hydraulic conductivity showed similar patterns of increase, although the water loss in xylem increased markedly at -5.0 MPa or less. One seedling that had reached 72% loss of the water-conducting area survived and the xylem water potential recovered to -0.3 MPa. We concluded that Japanese black pines may need to maintain water-filled tracheids within earlywood of the current-year xylem under natural conditions to avoid disconnection of water movement between the stem and the tops of branches. It is necessary to determine the spatial distribution of embolisms around the point of the lethal threshold to gain an improved understanding of plant survival under conditions of drought.

Background Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) are used to treat patients with non‐small cell lung cancer (NSCLC) and EGFR driver mutations. Although some patients discontinued these treatments because of adverse events, it is unclear whether switching EGFR‐TKI because of adverse events provides a benefit. Methods This retrospective study evaluated data from 22 patients with EGFR mutation‐positive NSCLC who received at least two EGFR‐TKIs that were switched because of adverse events (March 2011 to September 2017). Progression‐free survival 2 (PFS2) was defined as the time from starting of the first EGFR‐TKI treatment to disease progression during the second EGFR‐TKI treatment. Results Seventeen patients received gefitinib as the first EGFR‐TKI treatment, while four patients received afatinib and one patient received erlotinib. The median time to failure of the first EGFR‐TKI treatment was 1.6 months. The EGFR‐TKIs were switched because of hepatotoxicity (n = 16), interstitial lung disease (n = 3), and other reasons (n = 3). The median washout period was 1.1 months. Seventeen patients received erlotinib as the second EGFR‐TKI treatment, while three patients received gefitinib and two patients received afatinib. The median PFS for the second EGFR‐TKI treatment was 15.2 months. The median PFS2 was 17.7 months and the median overall survival was 32.8 months. Conclusions Switching EGFR‐TKIs because of adverse events provided a clinical benefit for patients with EGFR mutation‐positive NSCLC. Appropriate judgment regarding switching from one EGFR‐TKI to another may improve the performance status and prognosis of patients with EGFR mutation‐positive NSCLC.

Objective Superior mesenteric artery (SMA) syndrome is characterized by the compression of the third segment of the duodenum between the SMA and aorta, resulting in duodenal obstruction. Because the symptoms of the syndrome are similar to those of functional dyspepsia (FD), this study aimed to examine whether or not patients with SMA syndrome were present among those diagnosed with FD. Methods Patients with an FD diagnosis underwent measurement of the angle and distance between the SMA and aorta by ultrasonography or computed tomography. Patients with an angle of ≤22° or with a distance of ≤8 mm between the SMA and aorta were diagnosed with SMA syndrome. Bacterial culture of the duodenal aspirate was also performed. Results Of the 46 FD patients, 5 (11%) met the criteria. All 5 were women with a body mass index significantly lower than the remaining 41 patients (18.7 vs. 24.0 kg/m2, p=0.003). In addition, all 5 patients had 105/mL or more bacteria in the duodenum. The symptoms of these five patients were treated through dietary and postprandial posture counselling with or without medication. Conclusion Patients with SMA syndrome were observed among underweight women diagnosed with FD. Their symptoms may be associated with bacterial overgrowth.

This study evaluated variation in the height at which absent rings and internodes were detected along stem of Abies sachalinensis trees grown under shade for 39 years. Eight sample trees planted in 1974 under a secondary forest in Japan were felled in 2013 and analyzed. A. sachalinensis is a monopodial species in which it is possible to measure annual apical growth using the distinct internodes. We applied microscopic analysis on 154 stem disks from the stem base to the top to evaluate the cessation of apical and radial growth caused by intensive shading. Cessation of apical stem growth for one or more years was found in 6 out of 8 sample trees. We termed this phenomenon as “absent internode”. In addition, the absent growth rings were detected more frequently in the lower part of sample stems, and the number of absent rings at the stem base did not correspond with the number of absent internodes in the six trees. From cellular level observation, the five suppressed trees had no living cambial cells at the stem base but had living cells at the stem top. The cessation of the apical and radial growth did not occur synchronously but did occur independently under a shade environment in A. sachalinensis.

Background A combination of hepatitis B immunoglobulin and nucleos(t)ide analogues is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation (OLT). However, frequent immunoglobulin treatment is expensive and inconvenient. This study investigated the efficacy of hepatitis B virus (HBV) vaccination in preventing the recurrence of hepatitis B after living donor OLT. Methods Twenty-seven patients who had undergone living donor OLT participated in the study; five had acute HBV infected liver failure (ALF-OLT) and 22 had HBV related liver cirrhosis (LC-OLT). Hepatitis B surface antigen (HBsAg)-containing vaccine was administered to them for at least 1 year after transplantation and continued once monthly for up to 36 months post-OLT. Patients who had anti-HBs antibody titers above 100 mIU/mL for a minimum of 6 months without immunoglobulin administration were defined as good responders; the others were defined as poor responders. Interferon-γ enzyme-linked immunospot assays against HBs and HBc antigens were used to assay cellular immune responses. Results All five of the ALF-OLT patients had good responses after a median of four (range 2.5–5) vaccinations. Nine of the 22 LC-OLT patients had good responses after a median of 19 (range 11.5–30) vaccinations. Among the LC-OLT group, those with livers donated by relatively higher-aged, marital and high-titer anti-HBs antibody donors were good responders. LC-OLT patients classed as good responders showed interferon-γ responses comparable to those of the ALF-OLT patients. Conclusions The ALF-OLT and LC-OLT patients who received livers from relatively higher-aged, marital, high-titer anti-HBs antibody donors were the best candidates for HBV vaccine administration. Boosting donors before transplantation may facilitate later vaccine response of the recipients.

Alectinib is a second-generation inhibitor of anaplastic lymphoma kinase (ALK) and has been approvedfor the treatment of ALK-positive non-small cell lung cancer (NSCLC) in Japan since 2014. Particularly, alectinib has promising efficacy against central nerve system (CNS) metastases in patients with pretreated ALK-positive NSCLC. Nevertheless, interstitial lung disease (ILD) is one of the serious adverse events reported in some case reports, and these cases led to the discontinuation of alectinib therapy. Crizotinib is a first-generation ALK inhibitor that sometimes develops ILD, as reported with alectinib. However, according to previous studies, some patients with crizotinib-induced ILD who could continue crizotinib therapy. Herein, we report the cases of eight patients with ALK-positive NSCLC treated with alectinib. All patients achieved disease control including seven partial responses. Of five patients with CNS metastases at baseline, all patients had an objective response. In a partial response case, a 67-year-old woman with leptomeningeal metastasis at baseline developed asymptomatic ILD one year after alectinib induction. We continued alectinib carefully, and ILD slightly improved naturally, as observed on computed tomography. This case indicated that some patients with alectinib-induced ILD may be able to continue alectinib therapy.

Purpose Acute respiratory distress syndrome is a life-threatening form of respiratory failure without an established pharmacological treatment. Recently, macrolides have been found to be beneficial in cases of acute lung injury, but evidence is limited. Materials and methods This single-centre retrospective cohort evaluation of hospitalized patients with sepsis-associated acute respiratory distress syndrome aimed to assess the impact of azithromycin on clinical outcomes by using a propensity score analysis. All data were collected prospectively as part of ongoing research on high-resolution computed tomography of acute respiratory distress syndrome. The primary outcome was 60-day mortality; the secondary outcome was the number of ventilator-free days. Results Twenty-nine of 125 patients with sepsis-associated acute respiratory distress syndrome (23.2 %) received azithromycin within 24 h after acute respiratory distress syndrome diagnosis. After adjusting for potentially confounding covariates, azithromycin use was associated with lower 60-day mortality (hazard ratio, 0.31; 95 % confidence interval, 0.11–082; P = 0.02) and a shorter time to successful discontinuation of mechanical ventilation. Conclusions Azithromycin use was associated with decreased mortality and ventilator dependency in patients with sepsis-associated acute respiratory distress syndrome. Further well-designed prospective studies are needed. Electronic supplementary material The online version of this article (doi:10.1186/s40064-016-2866-1) contains supplementary material, which is available to authorized users.

Objectives To investigate subcutaneous blood flow rate (SBFR) in healthy volunteers and patients with severe motor and intellectual disabilities (SMID), and evaluate the effect of mentholated warm compresses (MWCs) on SBFR and subcutaneous ceftazidime absorption in healthy volunteers. Methods SBFR at the forearm, chest and abdomen were evaluated in Japanese healthy volunteers and in adults with SMID. The effects of MWCs on blood flow rate and ceftazidime pharmacokinetics were evaluated in healthy volunteers. Results SBFR was significantly lower in the forearms of female patients with SMID (n?=?11) than in the forearms of healthy females (n?=?6); it was not significantly lower in the abdomen or chest. There were no significant differences between male patients (n?=?18) or controls (n?=?12) in SBFR at any site. MWC application increased SBFR 1.3- to 2.0-fold compared with baseline in healthy controls (n?=?6). MWC application increased ceftazidime maximum blood concentration, SBFR and time above mutant prevention concentration in a single healthy subject. Conclusions Abdominal SBFR in patients with SMID did not differ from that of healthy subjects. MWC application increases SBFR and subcutaneous drug absorption rate in healthy humans., Open Access.

Alkaline phosphatase (ALP) flare phenomenon documented as scintigraphic flare phenomenon due to elevated serum ALP levels produced by osteoblasts reflects an osteoblastic reaction in response to the effective therapy of non-small cell lung cancer (NSCLC). Here, we report a case of ALP flare following gefitinib treatment for NSCLC. We also retrospectively analyzed the prevalence of ALP flare in lung cancer patients treated via epidermal growth factor receptor-tyrosine kinase inhibitor in our hospital. Recognition of this phenomenon is important for physicians treating NSCLC patients to avoid discontinuation of a potentially beneficial treatment because of misdiagnosis for refractory multiple bone metastasis or adverse effect.

The cytokine IL-15 and the inhibitor of DNA binding (Id)2, which negatively regulates the activity of basic helix-loop-helix transcription factors, have been shown to play key roles in NK cell development. Consistent with this, exogenous IL-15 added to human thymic progenitor cells stimulated their development into NK cells at the expense of T cells both in fetal thymic organ culture and in coculture with stromal cells expressing the Notch ligand Delta-like 1. Overexpression of Id2 in thymic progenitor cells stimulated NK cell development and blocked T cell development. This, in part, is attributed to inhibition of the transcriptional activity of the E protein HEB, which we show in this study is the only E protein that enhanced T cell development. Notably, Id2 increased a pool of lineage CD1a–CD5+ progenitor cells that in synergy with IL-15 furthered expansion and differentiation into NK cells. Taken together, our findings point to a dualistic function of Id2 in controlling T/NK cell lineage decisions; T cell development is impaired by Id2, most likely by sequestering HEB, whereas NK cell development is promoted by increasing a pool of CD1a–CD5+ NK cell progenitors, which together with IL-15 differentiate into mature NK cells.