Incidence, etiology, and outcome of hospital-acquired pneumonia in patients with acute exacerbation of fibrotic idiopathic interstitial pneumonia.

BACKGROUND: Acute exacerbations (AEs) of fibrotic idiopathic interstitial pneumonia (fIIP) that require hospitalization occur in some patients. During hospitalization, these patients can develop hospital-acquired pneumonia (HAP), a common hospital-acquired infection with a high mortality rate. However, the characteristics of HAP in AE-fIIP remain unknown. The purpose of this study was to determine the incidence, causative pathogens, and outcomes of HAP in patients with AE-fIIP. METHODS: The medical records of consecutive patients who were hospitalized with AE-fIIP from January 2008 to December 2019 were analyzed for the incidence, causative pathogen, and survival of HAP. The records of patients with an obvious infection-triggered AE were excluded from analysis. RESULTS: There were 128 patients with AE-fIIP (89 with idiopathic pulmonary fibrosis [IPF] and 39 with non-IPF fIIP) who were hospitalized a total of 155 times (111 with IPF and 44 with non-IPF fIIP). HAP occurred in 49 patients (40 with IPF and 9 with non-IPF fIIP). The incidence and the in-hospital mortality rates of HAP in patients with AE-fIIP were high, at 32.2% and 48.9%, respectively. Corynebacterium spp. was the most common causative pathogen, which was followed by human cytomegalovirus (HCMV). CONCLUSIONS: The incidence and the in-hospital mortality rates of HAP in patients with AE-fIIP are high. To improve their survival, patients with fIIP who had AEs and HAP should receive prompt empirical treatment for possible infections with Corynebacterium spp. and testing for HCMV.

Role of bronchial hyperresponsiveness in patients with obstructive sleep apnea with asthma-like symptoms.

BACKGROUND: Obstructive sleep apnea (OSA) is one of the major co-morbidities and aggravating factors of asthma. In OSA-complicated asthma, obesity, visceral fat, and systemic inflammation are associated with its severity, but the role of bronchial hyperresponsiveness (BHR) is unclear. We investigated the involvement of BHR and mediastinal fat width, as a measure of visceral fat, with OSA severity in patients with OSA and asthma-like symptoms. METHODS: Patients with OSA who underwent BHR test and chest computed tomography scan for asthma-like symptoms were retrospectively enrolled. We evaluated the relationship between apnea-hypopnea index (AHI) and PC20 or anterior mediastinal fat width, stratified by the presence or absence of BHR. RESULTS: OSA patients with BHR (n = 29) showed more obstructive airways and frequent low arousal threshold and lower mediastinal fat width, and tended to show fewer AHI than those without BHR (n = 25). In the overall analysis, mediastinal fat width was significantly positively correlated with AHI, which was significant even after adjustment with age and gender. This was especially significant in patients without BHR, while in OSA patients with BHR, there were significant negative associations between apnea index and airflow limitation, and hypopnea index and PC20. CONCLUSIONS: Risk factors for greater AHI differed depending on the presence or absence of BHR in OSA patients with asthma-like symptoms. In the presence of BHR, severity of asthma may determine the severity of concomitant OSA.

Diaphragm dome height on chest radiography as a predictor of dynamic lung hyperinflation in COPD.

Background and objective: Dynamic lung hyperinflation (DLH) can play a central role in exertional dyspnoea in patients with COPD. Chest radiography is the basic tool for assessing static lung hyperinflation in COPD. However, the predictive capacity of DLH using chest radiography remains unknown. This study was conducted to determine whether DLH can be predicted by measuring the height of the right diaphragm (dome height) on chest radiography. Methods: This single-centre, retrospective cohort study included patients with stable COPD with pulmonary function test, cardiopulmonary exercise test, constant load test and pulmonary images. They were divided into two groups according to the median of changes of inspiratory capacity (ΔIC=IC lowest - IC at rest). The right diaphragm dome height and lung height were measured on plain chest radiography. Results: Of the 48 patients included, 24 were classified as having higher DLH (ΔIC ≤-0.59 L from rest; -0.59 L, median of all) and 24 as having lower DLH. Dome height correlated with ΔIC (r=0.66, p<0.001). Multivariate analysis revealed that dome height was associated with higher DLH independent of % low attenuation area on chest computed tomography and forced expiratory volume in 1 s (FEV1) % predicted. Furthermore, the area under the receiver operating characteristic curve of dome height to predict higher DLH was 0.86, with sensitivity and specificity of 83% and 75%, respectively, at a cut-off of 20.5 mm. Lung height was unrelated to ΔIC. Conclusion: Diaphragm dome height on chest radiography may adequately predict higher DLH in patients with COPD.

Prognostic value of the qSOFA in patients with acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) have a slowly progressive clinical course, although some develop acute exacerbations (AEs). An easily obtained composite score is desirable for predicting the survival rate in patients with AE of IPF (AE-IPF). We investigated the quick sequential organ failure assessment (qSOFA), originally developed to identify sepsis, as a predictor of mortality in patients with AE-IPF and compared it to other composite assessments. METHODS: Consecutive patients with IPF admitted for their first AE between 2008 and 2019 were recruited retrospectively. The association between the qSOFA score obtained at admission and mortality was investigated. RESULTS: During the study period, 97 patients with AE-IPF were hospitalized. The hospital mortality was 30.9%. Multivariate logistic regression analysis revealed that both the qSOFA and the Japanese Association for Acute Medicine (JAAM)-disseminated intravascular coagulation (DIC) scores were significant predictors of hospital mortality (odds ratio [OR] 3.86, 95% confidence interval [CI] 1.43-10.3; p = 0.007 and OR 2.71, 95% CI 1.56-4.67; p = 0.0004; respectively). Kaplan-Meier survival curves showed that both scores were consistently associated with survival. Furthermore, the sum of the two scores was a more effective predictor than the individual scores. CONCLUSIONS: The qSOFA score of patients admitted with AE-IPF was associated with both in-hospital and long-term mortality, which was also true for the JAAM-DIC score. The qSOFA score plus the JAAM-DIC score should be determined during the diagnostic evaluation of a patient with AE-IPF. Both scores combined may be more effective at predicting outcomes than individual scores.

Refractory Eosinophilic Granulomatosis with Polyangiitis Complicated with IgG4-related Disease Showing Different Treatment Responses for Each Organ.

We herein report a 75-year-old woman who presented with dyspnea and purpura. She was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) based on axonal damage observed in the left tibial nerve and skin and lung pathologies. Lung pathology showed IgG4-positive plasma cells, considered a complication of IgG4-related disease (IgG4-RD). Computed tomography revealed thickening of the abdominal aorta and a poor contrast area in the left kidney, which was indicative of IgG4-RD. Steroid administration improved the IgG4-RD. However, the EGPA resisted treatment; therefore, immunosuppressive drugs and mepolizumab were administered. Refractory EGPA complicated with IgG4-RD showed different treatment responses for each organ.

Detection of Changes in Monoamine Neurotransmitters by the Neonicotinoid Pesticide Imidacloprid Using Mass Spectrometry.

Monoamine neurotransmitters (MAs), including dopamine (DA) and serotonin (5-HT), regulate brain functions such as behavior, memory, and learning. Neonicotinoids are pesticides that are being used more frequently. Neonicotinoid exposure has been observed to produce neurological symptoms, such as altered spontaneous movements and anxiety-like behaviors, which are suspected to be caused by altered MA levels. However, current neurotoxicity tests are not sufficiently sensitive enough to make these determinations. In this study, we performed some behavior tests, and derivatization reagents to improve the ionization efficiency, which was applied to liquid chromatography mass spectrometry (LC-MS/MS) to reveal the effect of neonicotinoid administration on MAs in the brain. We orally administered the neonicotinoid imidacloprid (0, 10, and 50 mg/kg body weight) to C57BL/6NCrSlc mice. In the behavior tests, a decrease in activity was observed. The LC-MS/MS quantification of MAs in various brain regions showed a decrease in some MA levels in the olfactory bulb and the striatum. These results showed, for the first time, that even a low dose of imidacloprid could alter MA levels in various parts of the brain.

A new method for assessing lung tumor motion in radiotherapy using dynamic chest radiography.

Dynamic chest radiography (DCR) is a recent advanced modality to acquire dynamic and functional images. We developed a new method using DCR and the free analysis software, Kinovea, to assess lung tumor motion. This study aimed to demonstrate the usefulness of our method. Phantom and clinical studies were performed. In the phantom study, dynamic images of a moving lead sphere were acquired using DCR, and the motion of the phantom was tracked using Kinovea in a DCR video. The amplitude of phantom motion was measured and compared with a predetermined baseline amplitude. In a clinical study, DCR and respiratory-gated four-dimensional computed tomography (4D-CT) were performed on 15 patients who underwent stereotactic body radiation therapy for lung tumors. The amplitudes of tumor motion in DCR and 4D-CT were measured in the superior-inferior (SI), left-right (LR), and anterior-posterior (AP) directions, and the square root of the sum of squares (SRSS) of the amplitude was calculated in all directions. Spearman's rank correlation and the Wilcoxon signed-rank test were performed to determine the correlations of the amplitudes of tumor motion obtained using DCR and 4D-CT. In the phantom study, the absolute mean error between the measured and predetermined amplitudes was 0.60 mm (range: 0.061.53 mm). In the clinical study, the amplitudes of tumor motion obtained using DCR correlated significantly with those of 4D-CT in the SI and LR directions, as did the SRSS values. The median amplitudes for DCR were significantly higher than those for 4D-CT in all (SI, LR, and AP) directions, as were the SRSS values. Our proposed method based on DCR and Kinovea is useful for assessing lung tumor motion, visually and quantitatively. Therefore, DCR has potential as a new modality for evaluating lung tumor motion in radiotherapy.

Outcome of patients who were incidentally diagnosed with idiopathic pulmonary fibrosis: How early in the disease should we identify patients?

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is diagnosed incidentally in some patients with minimal or no respiratory symptoms. The clinical features of such patients are unknown. Herein we aimed to clarify the prevalence, clinical course, and prognostic factors of patients who were incidentally diagnosed with IPF. METHODS: The files of consecutive patients with newly diagnosed IPF were retrospectively reviewed to determine the methods involved in their diagnosis, and their outcomes. RESULTS: Among a total of 107 patients with newly diagnosed IPF, 35 (32.7%) were diagnosed incidentally, including 18 undergoing annual health check-ups and 17 undergoing assessment for other medical problems. The median survival from the time of diagnosis was 4.9 years for the 35 patients diagnosed incidentally, which was comparable to the median survival of 3.9 years for the 72 who were not diagnosed incidentally. The body mass index (BMI) was the sole independent predictor of survival (hazard ratio 0.78, 95% confidence interval 0.65-0.93, p = 0.006) in patients diagnosed incidentally. CONCLUSIONS: Nearly one third of patients with IPF were diagnosed incidentally, and their survival was still poor. Identifying patients during the earliest stage of IPF, particularly those with a low BMI, is warranted.

High source-sink ratio at and after sink capacity formation promotes green stem disorder in soybean.

Green stem disorder (GSD) of soybean is characterized by delayed leaf and stem maturation despite normal pod maturation. Previous studies have suggested that GSD occurrence is promoted by a high source-sink ratio, which is produced by thinning or shade removal at the R5 growth stage (the beginning of seed filling). Here the effects of different times and durations of shade removal after the R5 stage on GSD severity were analyzed. First, shade removal for more than 28 days after R5 increased GSD severity by more than 0.4 point in GSD score. Thinning treatment at R5 increased specific leaf weight by 23%, suppressed stem dry weight reduction, and upregulated 19 genes including those encoding vegetative storage proteins at R5 + 28d, indicating excess source ability relative to sink size. On the contrary, shade removal for 14 days after R5 decreased GSD severity by 0.5 point in GSD score. In this treatment, seed size was smaller, while seed number was significantly larger than control, suggesting that shortage of source ability relative to sink size. These results implied that soybean plants regulate GSD occurrences either positively or negatively according to a source-sink ratio during the R5 to R5 + 28d growth stages.

A Novel Exercise Facilitation Method in Combination with Cognitive Behavioral Therapy Using the Ikiiki Rehabilitation Notebook for Intractable Chronic Pain: Technical Report and 22 Cases.

Recent clinical practice guidelines for chronic pain indicate, with a high evidence level, that the combination of exercise and cognitive behavioral therapy (CBT) is effective. The purpose of this study was to evaluate the effectiveness of an exercise facilitation method in combination with CBT using the "Ikiiki Rehabilitation Notebook" for patients with intractable chronic pain. "Ikiiki" means active in Japanese. A total of 22 cases with chronic low back (n = 13), lower extremity (n = 8), or neck (n = 1) pain were treated using this notebook. Two cases dropped out, leaving 22 cases. Each case was evaluated in terms of the numerical rating scale (NRS) of the pain, activities of daily living (ADL), pain catastrophizing scale (PCS), and quality of life (QOL) at pretreatment and post-treatment. The endpoint of the method was to achieve the long-term goals set by the patients. The mean treatment period was 11.2 months. The outcomes were as follows: improvement of presenteeism: nine cases; enhanced participation in hobbies: seven cases; improved school attendance: two cases; return to work: one case; improvement of self-care and/or self-efficacy: three cases. The NRS, ADL, PCS, and QOL were significantly improved after the treatment. This method is possibly valuable for educating patients about the cause and treatment of chronic pain and actively facilitating exercise and social participation. Further studies are needed to investigate the effectiveness of using this notebook for the patient with intractable chronic pain.

Clinical implications of bronchoscopy for immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer.

BACKGROUND: The utility of bronchoscopy for patients with suspected immune checkpoint inhibitor (ICI)-related pneumonitis is currently debatable. The purpose of this study was to examine the findings of bronchoalveolar lavage (BAL) analysis and transbronchial lung biopsy (TBLB) in non-small cell lung cancer (NSCLC) patients with ICI-related pneumonitis, and to elucidate the clinical significance of bronchoscopy for this health condition. PATIENTS AND METHODS: Consecutive NSCLC patients treated with ICIs, diagnosed with ICI-related pneumonitis after undergoing bronchoscopy between October 2015 and March 2019 were retrospectively screened. Findings of BAL fluid analysis and/or TBLB specimen histology were reviewed. RESULTS: Twelve patients underwent bronchoscopy for the diagnosis of ICI-related pneumonitis, ten of whom underwent BAL. An increase in the proportion of lymphocytes higher than 20% was observed in all ten patients. An increase in the proportion of neutrophils (> 10%) and eosinophils (> 10%) was observed in two and one patient, respectively. TBLB specimens were analyzed for eight patients. Major histologic findings included alveolitis in seven (87.5%) and organizing pneumonia (OP) in five (62.5%) patients. Other findings included acute lung injury and fibrosis. All twelve patients demonstrated favorable outcomes. CONCLUSION: A major characteristic of BAL analysis in ICI-related pneumonitis with NSCLC was an increased proportion of lymphocytes. The histologic features of lung tissue included alveolitis and/or OP. Acute lung injury and fibrosis were observed. Although the necessity of bronchoscopy should be determined on a case-by-case basis, it is necessary to assess these parameters when proper differential diagnosis is needed.

Local Anesthetics Inhibit Transient Receptor Potential Vanilloid Subtype 3 Channel Function in Xenopus Oocytes.

BACKGROUND: The transient receptor potential vanilloid subtype 3 (TRPV3) channel is activated by innocuous temperature and several chemical stimuli. It is proposed to be involved in pathological pain development and is therefore considered a potential target for treating pain. Local anesthetics have been used for patients with both acute and chronic pain. Although blockage of the voltage-gated sodium channel is the primary mechanism by which local anesthetics exert their effects, they cannot be explained by this mechanism alone, especially in pathologic states such as chronic pain. Indeed, the effects of local anesthetics on multiple targets involved in the pain pathway have been reported. It has also been suggested that modulating the function of transient receptor potential (TRP) channels (eg, TRPV1 and transient receptor potential ankyrin 1 [TRPA1]) is one of the mechanisms of action of local anesthetics. However, the effects of local anesthetics on TRPV3 have not been reported. METHODS: We expressed TRPV3 in Xenopus oocytes and investigated the effects of local anesthetics on 2-aminoethoxydiphenyl borate (2APB)-induced currents using 2-electrode voltage-clamp techniques. RESULTS: Clinically used local anesthetics inhibited the 2APB-activated currents from the TRPV3 channel in a concentration-dependent manner at pharmacologically relevant concentrations with half maximal inhibitory concentration (IC50) values of 2.5 (lidocaine), 1.4 (mepivacaine), 0.28 (ropivacaine), and 0.17 (bupivacaine) mmol/L, respectively. Conversely, these local anesthetics also directly induced currents at higher concentrations, although these currents were quite small compared to the 2APB-induced currents. We found that the inhibition of TRPV3 by lidocaine is noncompetitive and independent of intracellular signaling cascades. 2APB-induced TRPV3 currents were reduced by extracellular N-(2,6-dimethylphenylcarbamoylmethyl) triethylammonium bromide (QX-314) but not by intracellular QX-314 nor benzocaine. Moreover, lidocaine showed a use-dependent block in TRPV3 inhibition. Finally, QX-314 appeared to slightly permeate the activated TRPV3 channel pore based on examination of oocytes coexpressing TRPV3 and a sodium channel. These results suggest that local anesthetics could inhibit TRPV3 channel function by extracellular interactions of their charged forms with the channel pore. CONCLUSIONS: Local anesthetics inhibited TRPV3 2APB-induced currents at pharmacologically relevant concentrations when TRPV3 was expressed in Xenopus oocytes. These effects seem to occur via an extracellular interaction between the charged form of the anesthetic with the TRPV3 channel pore. These results help to elucidate the mechanisms of action of local anesthetics.

Initial therapeutic dose of corticosteroid for an acute exacerbation of IPF is associated with subsequent early recurrence of another exacerbation.

Some patients with idiopathic pulmonary fibrosis (IPF) undergo recurrent acute exacerbations (AEs). This study aimed to elucidate the risk factors for recurrent AEs of IPF (AE-IPF). Consecutive patients with IPF admitted for their first AE-IPF between January 2008 and December 2018 were retrospectively recruited. Of 63 patients admitted for an AE-IPF and discharged alive, 9 (14.3%) developed a recurrence of AE within 1 year. The mean time to recurrence was 233 ± 103 days. Total doses (mg/month and mg/kg/month) of corticosteroids administered over day 1 to 30 after the AE were significantly higher in patients without recurrences of AE-IPF (5185 ± 2414 mg/month, 93.5 ± 44.0 mg/kg/month) than the doses in patients with recurrences (3133 ± 1990 mg/month, 57.2 ± 37.7 mg/kg/month) (p = 0.02 and p = 0.03, respectively). However, no differences were observed between the total doses of corticosteroids administered over days 31 to 60, 61 to 90, 91 to 120, and 151 to 180 after the AE. Furthermore, differences between the administration rates of immunosuppressive and antifibrotic treatments administered to the 2 patient groups were not significant. An increased total dose of corticosteroid administered over day 1 to 30 after an AE-IPF was associated with a decreased risk of subsequent recurrence of AE-IPF within 1 year after the first AE.

Comparison of CURB-65, PSI, and qSOFA for predicting pneumonia mortality in patients with idiopathic pulmonary fibrosis.

Some patients with idiopathic pulmonary fibrosis (IPF) require hospitalization due to pneumonia. Although predictive scoring tools have been developed and validated for community-acquired pneumonia (CAP), their usefulness in IPF is unknown. The Confusion, Urea, Respiratory Rate, Blood Pressure and Age (CURB-65) score and the Pneumonia Severity Index (PSI) are validated for CAP. The quick Sequential Organ Failure Assessment (qSOFA) is also reported to be useful. The aim of this study was to investigate the ability of these tools to predict pneumonia mortality among hospitalized patients with IPF. A total of 79 patients with IPF and pneumonia were hospitalized for the first time between January 2008 and December 2017. The hospital mortality rate was 15.1%. A univariate logistic regression analysis revealed that the CURB-65 (odds ratio 4.04, 95% confidence interval 1.60-10.2, p = 0.003), PSI (4.00, 1.48-10.7, 0.006), and qSOFA (5.00, 1.44-1.72, 0.01) scores were significantly associated with hospital mortality. There was no statistically significant difference between the three receiver operating characteristic curves (0.712, 0.736, and 0.692, respectively). The CURB-65, PSI, and qSOFA are useful tools for predicting pneumonia mortality among hospitalized patients with IPF. Because of its simplicity, the qSOFA may be most suitable for early assessment.

Clinical course and prognosis in survivors of acute exacerbations of idiopathic pulmonary fibrosis.

BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) are at risk of acute exacerbations (AEs) that manifest as respiratory distress. However, the clinical course after AEs of IPF (AE-IPFs) has not been well described. Therefore, we aimed to elucidate the clinical course and prognosis in survivors of AE-IPFs. METHODS: Consecutive patients with IPF who presented to our institution with their first AE-IPFs between January 2008 and December 2019 were included in this study. Data were retrospectively collected, and the clinical course, survival, and cause of death were further analyzed. RESULTS: Ninety-seven patients were included in this retrospective study. Among them, 67 (69.1%) were discharged alive, with a median survival time after discharge of 1081 days. AE recurrence and pneumonia were the most common causes of death, each accounting for 22.2% of cases among survivors of AE-IPFs. AEs were the most frequent during the first 3 years after discharge, whereas pneumonia was more common thereafter. CONCLUSIONS: Survivors of AE-IPFs have a relatively favorable long-term prognosis. Among the survivors of first AE-IPFs, AE recurrence and pneumonia were the most common causes of death after discharge. Therefore, preventing AE recurrence and lung infections is crucial for prolonging survival in survivors of AE-IPFs.

A randomized controlled trial of long-acting muscarinic antagonist and long-acting ß2 agonist fixed-dose combinations in patients with chronic obstructive pulmonary disease.

BACKGROUND: In chronic obstructive pulmonary disease (COPD) patients, combination treatment with long-acting muscarinic antagonist (LAMA) and long-acting ß2 agonist (LABA) increases forced expiratory volume in one second and reduces symptoms compared to monotherapy. In Japan, three different once-daily fixed-dose combinations (FDCs) have been prescribed since 2015, although a direct comparison of these FDCs has never been performed. The objective of the present study was to compare the effectiveness, preference, and safety of three LAMA/LABA FDCs-glycopyrronium/indacaterol (Gly/Ind), umeclidinium/vilanterol (Ume/Vil), and tiotropium/olodaterol (Tio/Olo)-in patients with COPD. METHODS: We enrolled 75 COPD outpatients (male:female ratio, 69:6; 77.4 ± 6.9 years). A prospective, randomized, crossover study was conducted on three groups using three FDCs: Gly/Ind; Ume/Vil; and Tio/Olo. Each medication was administered for 4 weeks before crossover (total 12 weeks). After each FDC administration, a respiratory function test and questionnaire survey were conducted. A comparative questionnaire survey of all three LAMA/LABA FDCs was conducted after 12 weeks (following administration of final FDC). RESULTS: No significant differences in COPD Assessment Test or modified Medical Research Council dyspnea questionnaire were reported in the surveys completed after each FDC administration; no significant differences in spirometric items were observed. In the final comparative questionnaire survey, patients reported better actual feeling of being able to inhale following Gly/Ind administration compared with Tio/Olo, although no significant differences in adverse events or other evaluations were reported. CONCLUSIONS: The three LAMA/LABA FDCs administered to COPD patients show similar effects and safety, although some minor individual preference was reported. Trial registration This study retrospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000041342, registered on August 6, 2020).

HFpEF without elevated right ventricular systolic pressure is a favorable prognostic indicator in patients with IPF requiring hospitalization for heart failure.

BACKGROUND: Some patients with idiopathic pulmonary fibrosis (IPF) must be hospitalized because of heart failure (HF), including HF with preserved ejection fraction (HFpEF) and HF with reduced EF (HFrEF). The association between IPF and HF has not been clarified. We retrospectively investigated the clinical features and outcomes of patients with IPF who required nonelective hospitalization because of HF. METHODS: We examined data from IPF patients who required nonelective hospitalization for HF at the Kindai University Hospital from January 2008 to December 2018. We divided the patients into 3 groups: those with HFpEF without elevated right ventricular systolic pressure (RVSP), those with HFpEF and elevated RVSP, and those with HFrEF. The recurrence rates of HF after discharge and the 30- and 90-day mortality rates of the patients were evaluated. RESULTS: During the study period, 37 patients with IPF required hospitalization because of HF. Among the 34 patients included in the study, 17 (50.0%) were diagnosed with HFpEF without elevated RVSP, 11 (32.3%) with HFpEF and elevated RVSP, and 6 (17.6%) with HFrEF. Patients with HFrEF had significantly higher values for B-type natriuretic peptide (BNP) and left ventricular (LV) end-systolic and end-diastolic diameters than patients with the 2 types of HFpEF (BNP: P = 0.01 and P = 0.0004, LV end-systolic diameter: P <0.0001 and P <0.0001, and LV end-diastolic diameter: P = 0.01 and P = 0.0004, respectively). Notably, the difference between the LVEFs of the patients with 2 types of HFpEF was not significant. The patients with HFpEF without elevated RVSP had the lowest 30- and 90-day mortality rates (0%, P = 0.02 and 11.7%, P = 0.11, respectively). CONCLUSIONS: Among patients with IPF, HFpEF without elevated RVSP was the most common type of HF that required hospitalization. Patients with HFpEF without elevated RVSP survived longer than the patients with the other 2 types of HF.

Pneumothorax in patients with idiopathic pulmonary fibrosis: a real-world experience.

BACKGROUND: Some patients with idiopathic pulmonary fibrosis (IPF) develop pneumothorax. However, the characteristics of pneumothorax in patients with IPF have not been elucidated. The purpose of this study was to clarify the clinical course, actual management, and treatment outcomes of pneumothorax in patients with IPF. METHODS: Consecutive patients with IPF who were admitted for pneumothorax between January 2008 and December 2018 were included. The success rates of treatment for pneumothorax, hospital mortality, and recurrence rate after discharge were examined. RESULTS: During the study period, 36 patients with IPF were admitted with pneumothorax a total of 58 times. During the first admission, 15 patients (41.7%) did not receive chest tube drainage, but 21 (58.3%) did. Of the 21 patients, 8 (38.1%) received additional therapy after chest drainage. The respective treatment success rates were 86.6% and 66.7% in patients who underwent observation only vs chest tube drainage. The respective hospital mortality rates were 13.3% and 38.0%. The total pneumothorax recurrence rate after hospital discharge was 34.6% (n = 9). CONCLUSIONS: Pneumothorax in patients with IPF was difficult to treat successfully, had a relatively poor prognosis, and showed a high recurrence rate.

Chronic low-dose exposure to imidacloprid potentiates high fat diet-mediated liver steatosis in C57BL/6J male mice.

Hepatic steatosis is known to precede a continuum of events that lead to hepatic metabolic dysfunction, inflammation and carcinogenesis. Recently, studies have linked xenobiotic exposures to hepatic steatogenesis and its associated metabolic disorders; however, the underlying mechanisms remain elusive. This study aimed to elucidate the mechanistic role of imidacloprid in the prevalence of high fat diet (HFD)-induced liver steatosis, using a C57BL/6J mice model. Mice (3 weeks old) were fed with HFD and treated with 0.6 mg/kg bw/day (one-tenth of the NOAEL) of imidacloprid through water or diet, for 24 weeks. In a controlled group, mice were fed with only HFD. At the end of the study, imidacloprid treatment significantly potentiated HFD-induced body weight gain in mice. Also, imidacloprid increased the liver weights of mice, with complimentary reductions in mesenteric and gonadal white adipose tissue weights. Histopathological analysis of liver revealed a drastic steatosis in imidacloprid treated mice. Following a real-time qPCR analysis, imidacloprid upregulated transcriptions of hepatic fatty acid biosynthesis-related transcription factors and genes. Imidacloprid also induced hepatic expression of the gene encoding pregnane X receptor; but had no significant effect on hepatic expressions of liver X receptor and aryl hydrocarbon receptor. The imidacloprid treatment further enhanced serum alanine aminotransferase levels but downregulated hepatic antioxidant mRNA expressions. Ultimately, this study suggested an imidacloprid-potentiation effects on prevalence of HFD-induced liver steatosis via transcriptional modulations of the hepatic FA biosynthesis pathway.

Time Course in Ocular Blood Flow and Pulse Waveform in a Case of Ocular Ischemic Syndrome with Intraocular Pressure Fluctuation.

We report on a 70-year-old Japanese man with complaints of worsening left visual acuity who was diagnosed with ocular ischemic syndrome (OIS) associated with internal carotid artery (ICA) stenosis. A gonioscopy examination showed rubeosis iridis and elevated intraocular pressure (IOP) in the left eye (50 mmHg) at the baseline visit. The optic nerve head (ONH) and choroidal blood flow measured by laser speckle flowgraphy (LSFG) was impaired in the left eye compared with that in the right eye. Additionally, the blowout score (BOS), which indicates the variation of the mean blur rate (MBR) during systolic and diastolic periods, was decreased in the left eye. After treatment with an injection of bevacizumab and administration of Rho-associated kinase-inhibitor ripasudil eye drops, both ocular blood flow and BOS in each vascular bed gradually increased along with IOP reduction. The visual acuity also improved. The current case demonstrated increased blood flow and decreased fluctuation of blood flow in the ONH and choroid before and after the treatment in OIS with rubeosis iridis. The LSFG technique is useful to non-invasively assess the ocular circulation and pulse waveform in OIS.