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Background: Hypersensitivity pneumonitis (HP) is a complex and heterogenous interstitial lung disease (ILD) that occurs in susceptible individuals due to certain inhaled antigens. Fibrotic-HP is a major underlying disease of progressive pulmonary fibrosis. Therefore, in addition to the radiological features of HP, quantitatively measuring fibrosis is important to evaluate disease severity and progression. The present study aimed to compare three-dimensional computed tomography (3D-CT)-derived lung volumes (LVs) of patients with HP and determine its association with mortality risk. Methods: In this retrospective and multicenter cohort study, 126 patients diagnosed with HP (fibrotic, n = 72 and non-fibrotic, n = 54) with a confidence level higher than moderate were enrolled. Each lobe LV was measured using 3D-CT at the time of diagnosis and standardized using predicted forced vital capacity. The 3D-CT LV was compared with those of 42 controls and 140 patients with idiopathic pulmonary fibrosis (IPF). Results: Compared to patients with fibrotic-HP, the standardized total LV was significantly higher in controls and patients with non-fibrotic-HP and was similar in patients with IPF. Longitudinal analyses demonstrated that approximately half of the patients with fibrotic-HP had an annual decrease in total LV. Decreased total and lower-lobe LVs were associated with shorter survival, and were independently associated with mortality together with ongoing exposure to inciting antigens. A composite model consisting of ongoing exposure to inciting antigens and total or lower-lobe LV successfully classified mortality risk into three groups. Conclusions: Quantitatively measuring standardized LV can help determine disease severity, progression, and mortality risk in patients with fibrotic-HP.

Background: Food protein-induced enterocolitis syndrome caused by solid foods (Solid-FPIES) is a non-immunoglobulin E-mediated allergic disease characterized by delayed gastrointestinal symptoms. An oral food challenge (OFC) test, although necessary, can be inconclusive in cases with mild symptoms. Moreover, limited diagnostic marker availability highlights the need for novel surrogate markers. We aimed to examine the efficacy of fecal hemoglobin (FHb), lactoferrin (FLf), and calprotectin (FCp) over time in evaluating gastrointestinal inflammation degree in Solid-FPIES. Methods: This observational study included 40 patients and 42 episodes at Juntendo University Hospital and affiliated hospitals between October 2020 and March 2024 categorized into FPIES (12 patients with 11 egg yolk, 1 fish, and 1 soybean episodes), control (14 patients with 15 episodes), and remission (14 patients). Fecal tests were performed for 7 days following antigen exposure. The ratios of each value were divided by the baseline value and analyzed over time course. Results: The FPIES group had significantly higher peak ratios of all fecal markers than the control group (p

Abstract Background Interstitial pneumonia with autoimmune features (IPAF), which does not meet any of the criteria for connective tissue diseases (CTD), has been attracting an attention in patients with idiopathic interstitial pneumonia (IIP). However, the biomarkers that reflect the clinical course of these patients have not been fully elucidated. Objective To identify useful serum biomarkers reflecting CTD-related features and favorable prognoses in patients with IIP. Methods This was a post hoc analysis of a prospective and multicenter cohort study between 2015 and 2020. Newly diagnosed patients with IIP were consecutively enrolled, and 74 autoimmune features and autoantibodies were comprehensively checked during IIP diagnosis. Serum levels of CXCL10, CXCL1, CCL2, BAFF, angiopoietin-2, and leptin were evaluated at the time of IIP diagnosis. Results Two hundred twenty-two patients (159 men and 63 women) with IIP were enrolled. The median observation duration was 36 months. The median age was 71 years old, and median %forced vital capacity (FVC) was 84.1% at the time of IIP diagnosis. The proportion of patients who met the classification criteria for IPAF was 11.7%. In patients with high serum CXCL10, changes in both %FVC and %diffusion lung capacity for carbon monoxide at one year were significantly higher than those in patients with low CXCL10 (p = 0.014 and p = 0.009, respectively), whereas these changes were not significant for other chemokines and cytokines. High CXCL10 levels were associated with acute/subacute onset (p

Aim: Antigen (Ag) presentation by Ag-presenting cells (APCs) is the first step in the generation of adaptive humoral and cellular immune responses. However, there have been few studies on the effects of flavonoids on APC function. In this study, we examined the effects of five polymethoxyflavones, two isoflavones, and one flavanol on CD11c+ dendritic cell function. Methods: CD11c+ dendritic cells were differentiated from bone marrow cells by culturing with granulocyte macrophage-colony stimulating factor. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The Ag-presenting ability was determined by a mixed lymphocyte reaction assay. Expressions of MHC class II, CD40, CD80, and CD86 molecules on CD11c+ cells were determined by flow cytometric analysis. Lipopolysaccharide-induced inflammatory cytokines productions were determined by enzyme-linked immunosorbent assay. Results: The flavonoids used in the study did not show strong toxicity to CD11c+ cells. Nobiletin, heptamethoxyflavone, and genistein enhance Ag-presenting function. Nobiletin and heptamethoxyflavone increased the expression of MHC class II and CD80 molecules. A direct correlation between APC function and lipopolysaccharide-induced cytokine production was not found. Conclusions: The results of the in vitro study indicate that flavonoids, nobiletin, heptamethoxyflavone, and genistein regulate innate dendritic cell function.

Background Endovascular treatment of large ischemic cores is challenging. The severity of ischemic stress is assessed using the apparent diffusion coefficient (ADC). We aimed to evaluate the ADC in patients with a low Alberta Stroke Program Early CT [Computed Tomography] Score using diffusion‐weighted imaging and whether it correlates with clinical outcomes. Methods This study included consecutive patients with acute large ischemic stroke (Alberta Stroke Program Early CT Score‐diffusion‐weighted imaging ≤5) who underwent endovascular treatment with successful recanalization between April 2014 and March 2023. The most frequent ADC (peak ADC) and diffusion‐weighted imaging lesion volumes were assessed. The primary outcome was the 3‐month modified Rankin Scale (mRS) score. Good (mRS score, 0–3) and poor clinical outcomes (mRS score, 4–6) were compared to confirm whether ADC was associated with clinical outcomes. Results In total, 78 patients were enrolled in this study; 30 had an mRS score of 0 to 3 at 3 months. The peak ADC in these patients was significantly higher than that in patients with mRS scores of 4 to 6 (P = 0.0002). In multivariate analysis, peak ADC was strongly associated with good clinical outcomes (odds ratio, 1.231; P = 0.0135) rather than onset‐to‐recanalization time and ischemic core volume. The optimal peak ADC threshold for discriminating between the mRS groups was 520×10−6 mm2/s with a sensitivity of 75% and a specificity of 73%. Good clinical outcomes were more frequently observed in patients with peak ADC ≥520×10−6 mm2/s (P

Abstract Background Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder defined by cytopenia and is associated with an increased risk of transformation to acute myeloid leukemia (AML). The outcome of MDS is poor, so alternative therapeutic approaches are needed to improve survival. The inhibition of the DNA damage response pathway, including poly (ADP-ribose) polymerase-1 (PARP-1), has been approved to treat several cancers. In addition, WEE1, a nuclear kinase, is overexpressed in many cancers. Therefore, a WEE1 inhibitor combined with a PARP-1 inhibitor could inhibit the proliferation of MDS and AML. Methods We analyzed whether WEE1 was regulated in the progression of MDS and AML. We also evaluated the efficacy of MK-1775 (WEE1 inhibitor) and talazoparib (PARP-1 inhibitor). Results PARP-1 expression was higher in the AML cells than in the MDS cells. However, WEE1 expression remained unchanged. MK-1775 or talazoparib alone inhibited MDS and AML cells after 72 h, and cellular cytotoxicity and caspase 3/7 activity were increased. The combined use of MK-1775 and talazoparib produced superior efficacy than either drug alone and SKM-1 colony formation was reduced. Significant cell populations in the sub-G1 phase were found in the cell-cycle analyses. Additionally, γ-H2AX expression and caspase 3 activity were increased. The combined treatment also changed the mitochondrial membrane potential. Conclusions The combination of a WEE1 inhibitor and PARP-1 inhibitor had enhanced efficacy and is proposed as a new therapeutic option for patients with MDS or AML. Our findings have clinical implications for a potential novel therapeutic strategy for MDS and AML patients.

This study examines how the valence and argument of comments affect viewers’ attitudes toward and validation of a pseudo-scientific claim. We developed and tested a hypothesized model based on the elaboration likelihood model. Participants watched a video that introduced pseudo-scientific claims with others’ comments on the same screen. We assigned participants (n = 646) to a control condition with no message presentation and a message condition, with the message condition divided into four conditions based on a combination of valence and substantiveness of the comments. Structural equation modeling analysis revealed that valence affected both heuristic and systematic thought, while substantiveness influenced systematic thought. The negativity of the comments not only suppressed the positive impressions, which were irrelevant to the content, but also facilitated the examination of the reasoning for the pseudoscience claims in the video. Including substantive content in the comments also led to an examination of the rationale for pseudoscience claims. The model also showed that positive impressions irrelevant to the content increased validity judgments, the final positive attitude, and agreement to the pseudo-scientific claim, while examination of the rationale for the claims decreased them.

Background: Hand hygiene is recommended to travellers to prevent common travel-related illnesses such as diarrhoea and respiratory infection. For effective hygiene promotion interventions, we aimed to identify the personal characteristics associated with handwashing behaviour. Methods: Prospective observational studies consisting of pre- and post-travel surveys were conducted among Japanese university students studying abroad between 2016 and 2018 (n = 825; 6–38 travel days). Associations of age, sex, study major, and overseas travel experience with handwashing behaviour (5-point scale) were evaluated using ordinal logistic regression models, with adjustment for destination, travel duration, and psychological factors (risk perception of diarrhoea and concern about hygiene). Results: Among the participants in our analysis (n = 629), 28.0 % washed their hands before every meal while abroad. The male sex and no overseas travel experience were associated with decreased frequency of infrequent handwashing, even after adjusting for all potential confounding factors, whereas the study major was not associated. The adjusted odds ratios (95 % confidence intervals) were 0.74 (0.56–0.99) for men vs. women and 0.69 (0.52–0.93) for no overseas travel experience vs. overseas travel experience but not to the current destination. Conclusions: The lack of overseas travel experience correlated with handwashing frequency in both men and women. In addition to the travel destination, the male sex and no overseas travel experience should be highlighted in pretravel hand hygiene interventions.

This study sought to develop a short DNA detection method using a deoxyuridine probe and polymerase chain reaction. The probe was hybridized to the target short DNA, which was then extended by DNA polymerase. The extended DNA was used for real-time PCR after the probe was removed by uracil DNA glycosylase. This method measured from 0.01 to 10 nM of a model short DNA sequence of 17 nucleotides. The method was then used to detect the nucleic acid medicine fomivirsen, as well as 21 phosphorothioate nucleotides, and to quantify 0.1–100 nM of fomivirsen. This method may be useful for detecting short DNA fragments, such as functional nucleotides.

Evaluation of access routes and shunting points plays a crucial role in the treatment of cavernous sinus dural arteriovenous fistulas (CS-dAVF). Generally, these evaluations are performed using three-dimensional rotation angiography. However, assessing access routes becomes challenging in cases lacking anterior or posterior drainage routes. Zero TE magnetic resonance imaging (MRI) is an innovative technique enabling the visualization of cortical bone. By merging fusion images of zero TE and contrast-enhanced T1 weighted imaging (CE-T1WI), enhanced arteries can be visualized, resembling cranial bone-like three-dimensional rotation angiography. To determine the usefulness of fusion images in evaluating access routes and shunting points for dural arteriovenous fistulas, a comparison was made between these fusion images and three-dimensional rotation angiography in the same case. This report describes the application of fusion images in evaluating access routes and shunting points.

Abstract Background Acute exacerbation (AE) of systemic autoimmune disease-related interstitial lung diseases (SAID-ILD) is less common than AE of idiopathic pulmonary fibrosis (IPF) and the details of AE-SAID-ILD have not been elucidated, but the prognosis is similarly devastating. This study was undertaken to determine the incidences of AE-ILD in each SAID and to elucidate the proportion of progressive fibrosing (PF)-ILD in AE-SAID-ILD. Methods We retrospectively analysed data for patients with SAID-ILD who were diagnosed and observed at our hospital between 1999 and 2020. Results Two hundred and thirty-two patients with SAID-ILD were enrolled, with a mean observation period of 100.2 months. AE-SAID-ILD was found in 25 patients (10.78%), mainly in patients with RA (17 patients, 68%) and elderly male patients with a smoking history. The overall incidence of AE-SAID-ILD was 1.29%/person-year, and the incidence for each SAID was as follows: RA 2.193, microscopic polyarteritis (MPA) 3.203, systemic sclerosis (SSc) 2.277, primary Sjögren syndrome 0.426, and polymyositis/dermatomyositis 0.222. The incidence of AE of RA/MPA/SSc-ILD was significantly higher than that of other AE-SAID-ILD (p

Abstract Background The assessment of lung physiology via pulmonary function tests (PFTs) is essential for patients with idiopathic pulmonary fibrosis (IPF). However, PFTs require active participation, which can be challenging for patients with severe respiratory failure, such as during moments of acute exacerbation (AE) of IPF. Recent advances have enabled the re-construction of 3-dimensional computed-tomography (3D-CT) images. This study established a standardisation method and quantitative analysis of lung volume (LV) based on anthropometry using 3D-CT images. Methods This is a retrospective multi-center cohort study. The standardised 3D-CT LV in patients with IPF at diagnosis (n = 140) and during AE (cohort1; n = 61 and cohort2; n = 50) and those of controls (n = 53) were assessed. Results The standardised 3D-CT LVs at IPF diagnosis were less than those of control patients, especially in the lower lung lobes. The standardised 3D-CT LVs were correlated with forced vital capacity (FVC) and validated using the modified Gender-Age-Physiology (GAP) index. The standardised 3D-CT LVs at IPF diagnosis were independently associated with prognosis. During AE, PFTs were difficult to perform, 3D-CT analyses revealed reduced lung capacity in both the upper and lower lobes compared to those obtained at diagnosis. Lower standardised 3D-CT LVs during AE were independently associated with worse outcomes in the two independent cohorts. In particular, volume loss in the upper lobe at AE had prognostic values. Conclusions A novel image quantification method for assessing pulmonary physiology using standardised 3D-CT-derived LVs was developed. This method successfully predicts mortality in patients with IPF and AE of IPF, and may be a useful alternative when PFTs cannot be performed.

The pathogenesis of new visual symptoms after flow diverter stent placement in the ophthalmic artery for internal carotid artery aneurysms remains unclear. We report two cases of patients who developed visual field disturbance and decreased visual acuity following flow diverter placement. The “doughnut sign” was found around the optic nerve on magnetic resonance imaging.The patients had progressive visual field defects and impairment on the side where the flow diverter was placed. Short tau inversion recovery coronal images showed a doughnut-shaped high-signal around the optic nerve on the affected side. Both patients were treated with steroid pulse therapy, and 1 received endovascular therapy. Their symptoms gradually improved, and the “doughnut sign” disappeared.The “doughnut sign” observed around the optic nerve on magnetic resonance imaging may be found alongside visual disturbance symptoms after paraclinoid aneurysm treatment.It is recommended that short tau inversion recovery sequences be performed preoperatively in patients presenting with visual impairment and in whom the possibility of postoperative exacerbation is suspected.

Abstract The treatment of multiple myeloma (MM) patients has been dramatically changed by the introduction of new agents; however, many patients relapse. Hypoxia is a critical component of the bone-marrow microenvironment. 6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) is responsible for maintaining cellular levels of fructose-2,6-bisphosphate, which regulates glycolysis. We found that the gene expressions of PFKFB3 and PFKFB4 were elevated under hypoxic conditions. Treatments with the PFKFB3 inhibitor, PFK158, and PFKFB4 inhibitor, 5MPN, were found to inhibit the growth of myeloma cells. The combined treatment of myeloma cells with carfilzomib and PFK158 or 5MPN was more cytotoxic than either drug alone. Caspase 3/7 activity and cellular cytotoxicity were also increased. In addition, the combined treatment was effective in the bortezomib-resistant cell line. Our data also suggest that administration of PFKFB3 and PFKFB4 inhibitors may be a powerful strategy against myeloma cells and to enhance the cytotoxic effects of proteasome inhibitors in hypoxic conditions.

Abstract Background Mucociliary clearance (MCC) is an essential defense mechanism in airway epithelia for removing pathogens from the respiratory tract. Impaired ciliary functions and MCC have been demonstrated in asthma and chronic obstructive pulmonary disease (COPD). Long-acting muscarinic antagonists (LAMAs) are a major class of inhaled bronchodilators, which are used for treating asthma and COPD; however, the effects of LAMAs on ciliary function remain unclear. This study aimed to identify the effects of LAMAs on airway ciliary functions. Methods Wild-type BALB/c mice were treated with daily intranasal administrations of glycopyrronium for 7 days, and tracheal samples were collected. Cilia-driven flow and ciliary activity, including ciliary beat frequency (CBF), ciliary beating amplitude, effective stroke velocity, recovery stroke velocity and the ratio of effective stroke velocity to recovery stroke velocity, were analyzed by imaging techniques. Using in vitro murine models, tracheal tissues were transiently cultured in media with/without LAMAs, glycopyrronium or tiotropium, for 60 min. Cilia-driven flow and ciliary activity were then analyzed. Well-differentiated normal human bronchial epithelial (NHBE) cells were treated with glycopyrronium, tiotropium, or vehicle for 60 min, and CBF was evaluated. Several mechanistic analyses were performed. Results Intranasal glycopyrronium administration for 7 days significantly increased cilia-driven flow and ciliary activity in murine airway epithelium. In the murine tracheal organ culture models, treatment with glycopyrronium or tiotropium for 60 min significantly increased cilia-driven flow and ciliary activity in airway epithelium. Further, we confirmed that 60-min treatment with glycopyrronium or tiotropium directly increased CBF in well-differentiated NHBE cells. In the mechanistic analyses, neither treatment with glycopyrronium nor tiotropium affected intracellular calcium ion concentrations in well-differentiated NHBE cells. Glycopyrronium did not increase protein kinase A activity in well-differentiated NHBE cells. Moreover, glycopyrronium had no effect on extracellular adenosine triphosphate concentration. Conclusions LAMAs exert a direct effect on airway epithelium to enhance ciliary function, which may improve impaired MCC in asthma and COPD. Further investigations are warranted to elucidate the underlying mechanisms of the effects of LAMAs on the promotion of airway ciliary function.

(1) Background: Loneliness is inherently linked to social connections, with interpersonal communication playing a pivotal role. Despite this connection, limited research exists on the relationship between loneliness and communication among young adults. This study investigates the correlation between face-to-face, telephone, and online communication frequencies and loneliness among individuals in their 20s. (2) Methods: Using a dataset from a nationwide survey conducted by the Japanese Cabinet Office, this study focuses on 1812 respondents aged 20–30, selected from a random sample of 20,000 individuals aged 16 and older across Japan. (3) Results: A Multivariate Logistic Regression Analysis reveals a significant association between communication frequency and loneliness, even after adjusting for demographic characteristics. Notably, decreased communication frequency across all modalities correlated with increased loneliness. Online communication exhibited the highest impact, followed by face-to-face communication, with phone call communication ranking last. (4) Conclusions: This study emphasizes the importance of seamlessly integrating social networking service (SNS)-based communication with various forms of social interaction. A well-balanced integration of these approaches is crucial for mitigating loneliness among young individuals and promoting positive mental health outcomes.

Abstract Background The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial. Methods To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case–control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department. Results There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12). Conclusion This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases.

Abstract Background Multiple myeloma (MM) is a type of hematological malignancy affecting the functions of plasma cells. The treatment of MM patients has changed dramatically with the use of new agents. However, unfortunately, it is still incurable. Therefore, a new approach for treating MM is still needed to improve patient outcomes. Methods Because the histone deacetylase (HDAC) and phosphoinositide 3-kinase (PI3K) pathway is a key signal in cancer cell biology, we investigated whether dual HDAC and PI3K inhibitors could suppress the myeloma cells. Results Gene expression of HDACs is high in myeloma cells. CUDC-907, a dual inhibitor of PI3K and HDAC, inhibits HDAC activity. Akt activity and expression of BCL-XL, MCL-1, and NF-κB p65 were reduced by CUDC-907 in a dose-dependent manner. The number of apoptotic and caspase 3/7-positive cells also increased in the myeloma cells. Combined treatment of myeloma cells with carfilzomib and CUDC-907 increased cytotoxicity compared to that observed with each drug alone. Conclusions Data from this study suggested that the administration of CUDC-907 might be a powerful strategy against myeloma cells, to enhance the cytotoxic effects of proteasome inhibitors.

Pulmonary pleomorphic carcinoma (PPC) has an aggressive clinical course and poor prognosis mainly because of the difficulty in achieving therapeutic effects. Despite a small fraction of patients with PPC possessing an epidermal growth factor receptor (EGFR) activating mutation, only a limited number of studies have reported the efficacy of EGFR tyrosine kinase inhibitors in those patients. Here, we present successful treatment with first-line afatinib in a patient with EGFR mutation-positive, metastatic PPC.

We introduce our technique to treat dural arteriovenous fistulae (dAVFe) under sinus balloon protection. The Kaneka Shoryu 7 × 7 mm balloon was used for sinus occlusion. Initially, the balloon was inflated slowly using 1.5–2.0 mL of saline on the table. A 6F guiding catheter was navigated into the proximal portion of the lesion from the jugular vein of the affected side. The balloon catheter was introduced to the point occluding the shunt. The balloon was temporarily inflated to determine the occlusion point without occluding the outlet of the vein of Labbe. ONYX injection was started from the microcatheter located at just proximal to the shunt point under sinus balloon occlusion. ONYX penetrated the feeding arteries in an antegrade and retrograde manner. After the penetration of ONYX into each feeding artery, the inflated balloon was temporarily deflated to examine the residual shunt. If a small shunt remained, the balloon was inflated again and ONYX injection was continued. To cure dAVF, the location of the balloon is important. The guiding catheter should be placed just proximal to the shunt and the balloon catheter should be gently pulled to stabilize the balloon position.

Objective: Transarterial embolization under intrasinus balloon protection is an efficient treatment strategy for intracranial arteriovenous fistula. Ordinary balloon protection methods using the Copernic RC balloon may occlude the normal drainage route, and the occurrence of venous complications is concerning. The aim of this study was to report the efficacy of the supercompliant SHOURYU balloon catheter for intrasinus balloon protection while preserving the normal venous outlet. Methods: Eighteen patients with dural arteriovenous fistulas who were treated with transarterial embolization under intrasinus balloon protection between April 2011 and July 2020 were included. All lesions were treated with transarterial embolization under intrasinus balloon protection using the SHOURYU balloon catheter. Clinical and angiographic data were retrospectively collected, and the occlusion rate, complications, and clinical outcomes were analyzed. Results: Nine men and nine women were treated, and their average age was 61.1 years. Fistulas were located at the transverse-sigmoid sinus (n = 13), superior sagittal sinus (n = 3), tentorial sinus (n = 1), and around the torcular Herophili (n = 1). Ten patients were classified as Borden typeⅠand eight as Borden type Ⅱ. Complete (n = 9) or near-complete (n = 4) occlusion was achieved in 72.2% of the patients. Periprocedural complications, but no venous complications were observed in two patients. Symptoms were not aggravated after treatment. Conclusions: Transarterial embolization under intrasinus balloon protection using the SHOURYU balloon catheter is effective and safe for treatment of dural arteriovenous fistulas while maintaining the patency of the venous sinus.

Key Clinical Message Steroids used to treat sarcoidosis may induce aPAP. The cooccurrence of sarcoidosis and autoimmune pulmonary alveolar proteinosis (aPAP) is rare. In this case, aPAP merged into sarcoidosis regardless of the disease state of sarcoidosis and improved naturally. When using steroids during sarcoidosis exacerbation, attention should be paid to aPAP relapse.

We performed a prospective observational study of chronic myeloid leukemia (CML) patients after anti-SARS-CoV-2 BNT162b2 vaccination (VC). In total, 32 CML patients with tyrosine kinase inhibitor (TKI) therapy, 10 CML patients with treatment-free remission, and 16 healthy subjects participated in the study. From April 2021 to September 2021, all cases (median age = 58 years) were vaccinated twice. Immunoglobulin G for SARS-CoV-2 spike protein (S-IgG) was measured at three timepoints (before the first VC, 1–5 weeks after the second VC (T1), and approximately 6 months after the second VC (T2)). S-IgG was not observed before the first VC in any participant. At T1, all cases had acquired S-IgG. There were no significant differences in S-IgG levels among groups. A paired sample comparison of median S-IgG titers between T1 and T2 in all groups showed a significant reduction in T2 S-IgG titers. There were no significant differences in S-IgG levels among groups. When all patients were analyzed, those aged ≥58 years had significantly lower S-IgG levels than those aged

Accurate staging and evaluation of therapeutic effects are important in managing plasma-cell neoplasms. Diffusion-weighted imaging with body signal suppression magnetic resonance imaging (DWIBS-MRI) allows for acquisition of whole-body volumetric data without radiation exposure. This study aimed to investigate the usefulness of DWIBS-MRI in plasma-cell neoplasms. We retrospectively analyzed 29 and 8 Japanese patients with multiple myeloma and monoclonal gammopathy of undetermined significance, respectively, who underwent DWIBS-MRI. We conducted a histogram analysis of apparent diffusion coefficient values. The correlations between each histogram parameter and staging, cell maturation, prognosis, and treatment response were evaluated. We found that the apparent diffusion coefficient values in patients with monoclonal gammopathy of undetermined significance were lower than those in patients with multiple myeloma. Pretreatment apparent diffusion coefficient values of immature myeloma were lower than those of mature myeloma. Moreover, these values decreased in proportion to stage progression in Durie-Salmon classification system but showed no significant correlation with other staging systems or prognosis. Patients were stratified as responder, stable, and non-responder based on the International Myeloma Working Group criteria. The magnitude of changes in apparent diffusion coefficients differed significantly between responders and non-responders (0.154 ± 0.386 ×10-3 mm2/s vs. -0.307 ± 0.424 ×10-3 mm2/s, p = 0.003). Although its usefulness has yet to be established, DWIBS-MRI combined with apparent diffusion coefficient measurement allowed for excellent response evaluation in patients with multiple myeloma. Furthermore, apparent diffusion coefficient analysis using DWIBS-MRI may be useful in predicting cell maturation and total tumor volume.

Abstract Background Although therapeutic hypothermia improves the outcome of neonatal hypoxic-ischemic encephalopathy (HIE), its efficacy is still limited. This preliminary study evaluates the safety and feasibility of the combination therapy with erythropoietin (Epo), magnesium sulfate and hypothermia in neonates with HIE. Methods A combination therapy with Epo (300 U/kg every other day for 2 weeks), magnesium sulfate (250 mg/kg for 3 days) and hypothermia was started within 6 h of birth in neonates who met the institutional criteria for hypothermia therapy. All patients received continuous infusion of dopamine. Vital signs and adverse events were recorded during the therapy. Short-term and long-term developmental outcomes were also evaluated. Results Nine patients were included in the study. The mean age at first intervention was 3.9 h (SD, 0.5). Death, serious adverse events or changes in vital signs likely due to intervention were not observed during hospital care. All nine patients completed the therapy. At the time of hospital discharge, eight patients had established oral feeding and did not require ventilation support. Two patients had abnormal MRI findings. At 18 months of age, eight patients received a follow-up evaluation, and three of them showed signs of severe neurodevelopmental disability. Conclusion The combination therapy with 300 U/kg Epo every other day for 2 weeks, 250 mg/kg magnesium sulphate for 3 days and therapeutic hypothermia is feasible in newborn patients with HIE. Trial registration ISRCTN33604417retrospectively registered on 14 September 2018.

Although immune-checkpoint inhibitors (ICIs) have become an important choice of treatment for advanced NSCLC, recent reports show hyperprogressive disease (HPD) after ICI administration. The clinico-pathological features of HPD still remain unclear. Here we report a 65-year-old man with lung adenocarcinoma who abruptly presented HPD two days after pembrolizumab administration. The primary tumor increased in size from 40 mm to 57 mm on the chest HRCT. The patient died on day 37 after pembrolizumab administration. The autopsy demonstrated widespread progression of cancer cells into the alveolar spaces and lymphangitic carcinomatosis in the left lung, with plenty of bloody pleural effusion. We compared the pathohistology and immunohistochemical expression of PD-L1 between the pretreatment biopsy material and posttreatment autopsy materials, and found a change in PD-L1 expression which may be related to HPD. We also discuss the possibility of HPD, pseudoprogression, and interstitial lung disease when there is evidence of tumor growth or ground glass shadows on chest images after ICI treatment. Keywords: Hyperprogressive disease, Immune checkpoint inhibitors, Non-small cell lung cancer, PD-L1

Reports of chronic eosinophilic pneumonia (CEP) after radiation therapy are limited to breast cancer. We herein describe a case of CEP after radiation therapy for lung cancer. The patient was a 65-year-old man who had asymptomatic peripheral blood eosinophilia but no history of asthma or allergy. One month after completion of radiation therapy, chest CT scan revealed infiltrates inside the irradiated area, leading to the diagnosis of radiation pneumonitis. His condition improved after receiving corticosteroids. However, one months after withdrawal of corticosteroids, he noticed cough and shortness of breath with patchy ground glass opacity in the contralateral lung. The WBC count was 9900/μl with 17% eosinophils and bronchoalveolar lavage showed eosinophils of 14%, leading to the diagnosis of CEP. His condition improved after receiving corticosteroids and subsequent tapering without recurrence. Asymptomatic peripheral blood eosinophilia at the initial diagnosis of lung cancer might be a trigger for developing CEP.

Amiodarone is used commonly and effectively in the treatment of arrhythmia; however, it may cause thyrotoxicosis categorized into two types: iodine-induced hyperthyroidism (type 1 amiodarone-induced thyrotoxicosis (AIT)) and destructive thyroiditis (type 2 AIT). We experienced a case of type 2 AIT, in which high-dose steroid was administered intravenously, and we finally decided to perform total thyroidectomy, resulting in a complete cure of the AIT. Even though steroid had been administered to the patient (maximum 80 mg of prednisolone), the operation was performed safely and no acute adrenal crisis as steroid withdrawal syndrome was found after the operation. Few cases of type 2 AIT that underwent total thyroidectomy with high-dose steroid administration have been reported. The current case suggests that total thyroidectomy should be taken into consideration for patients with AIT who cannot be controlled by medical treatment and even in those under high-dose steroid administration.

BACKGROUND: The maternal mortality ratio in the Philippines remains high; thus, it will be difficult to achieve the Millennium Development Goals 5 by 2015. Approximately two-thirds of all maternal deaths occur during the postpartum period. Therefore, we conducted the present study to examine the current state of postpartum health care service utilization in the Philippines, and identify challenges to accessing postpartum care. METHODS: A questionnaire and knowledge test were distributed to postpartum women in the Philippines. The questionnaire collected demographical characteristics and information about their utilization of health care services during pregnancy and the postpartum period. The knowledge test consisted of 11 questions regarding 6 topics related to possible physical and mental symptoms after delivery. Sixty-four questionnaires and knowledge tests were analyzed. RESULTS: The mean time of first postpartum health care visit was 5.1 ± 5.2 days after delivery. Postpartum utilization of health care services was significantly correlated with delivery location (P

To assess the advantages of Adaptive Iterative Dose Reduction using Three Dimensional Processing (AIDR3D) for image quality improvement and dose reduction for chest computed tomography (CT).Institutional Review Boards approved this study and informed consent was obtained. Eighty-eight subjects underwent chest CT at five institutions using identical scanners and protocols. During a single visit, each subject was scanned using different tube currents: 240, 120, and 60 mA. Scan data were converted to images using AIDR3D and a conventional reconstruction mode (without AIDR3D). Using a 5-point scale from 1 (non-diagnostic) to 5 (excellent), three blinded observers independently evaluated image quality for three lung zones, four patterns of lung disease (nodule/mass, emphysema, bronchiolitis, and diffuse lung disease), and three mediastinal measurements (small structure visibility, streak artifacts, and shoulder artifacts). Differences in these scores were assessed by Scheffe's test.At each tube current, scans using AIDR3D had higher scores than those without AIDR3D, which were significant for lung zones (p

The overexpression of Twist and Slug and subsequent down-regulation of E-cadherin facilitate the acquirement of invasive growth properties in cancer cells. It is unclear which of these molecules are expressed in mesenchymal tumors in the central nervous system. Here, we investigated 10 cases each of hemangiopericytoma, solitary fibrous tumor, meningothelial, fibrous, angiomatous, and atypical meningiomas, and 5 cases of anaplastic meningioma for Slug, Twist, E-cadherin, and N-cadherin immunoexpression. Nuclear Slug expression was observed in 9/10 (90%) hemangiopericytomas and 5/10 (50%) solitary fibrous tumors, but not in any meningiomas, except for 1 case. Similarly, nuclear Twist expression was more extensive in hemangiopericytomas and solitary fibrous tumors than meningiomas. In contrast to Slug and Twist, the positive expression of E-cadherin was observed in 39/45 (87%) meningiomas, but not in any hemangiopericytomas or solitary fibrous tumors (P

Most pediatric intravenous anesthesia in Japan is performed outside the operating theatre by non-anesthetists. The 2020 revision increased reimbursement for long-term intravenous anesthesia (Category 3) by anesthesiologists, but its impact on practice behavior is unknown. We analyzed the annual number of calculations for each category of intravenous anesthesia and their age distribution from the national reimbursement data for the three-year period fiscal years (FY) 2018-20 to elucidate trends in the pediatric age group. Regional disparities of calculation rate of pediatric addition per capita were examined. According to FY 2019 statistics, 5,774 outpatient intravenous anesthesia and 50,686 inpatient intravenous anesthesia procedures were performed annually in patients under 15 years of age. Of these, no case was complex anesthesia (Category 3) performed by a specialist anesthesiologist in outpatient settings and 1,162(3.9%) in inpatient settings. Category 3 occupancy was slightly higher in infants and decreased with age. (P < 0.01) In FY 2020 data, 41(0.7%) new Category 3 procedure were calculated in outpatient cases. The share of Category 3 in inpatient cases decreased to 2.0%. There was no decrease in the number of overall venous anesthesia due to COVID-19 pandemic. Regional disparities in calculations were up to 20 times greater. Long-term total intravenous anesthesia by anesthesiologists is rarely performed in Japan. Improvements in reimbursement are not sufficient to enable total intravenous anesthesia by a specialized anesthesiologist. A system for safe intravenous anesthesia by non-anesthesiologists is needed. [ABSTRACT FROM AUTHOR]