Portal Vein Thrombosis With Hypoplasia in the Left Lobe of the Liver: A Case Report.

Portal vein thrombosis (PVT) is an acute-onset, emergent thrombotic disease that is difficult to diagnose without an apparent underlying disease unless the clinician actively suspects its presence. We present a case of acute PVT with underlying left lobe hypoplasia of the liver, a previously undescribed condition. A 79-year-old male patient presented to the emergency department with the chief complaint of anorexia. His medical history included hypertension and an old brain infarction. The patient had no history of surgery. Contrast-enhanced CT revealed the disappearance of the left lobe of the liver and defects in the contrast effect in the left portal vein. The diagnosis reached was PVT with left lobe hypoplasia of the liver. Hypoplasia of the liver manifests few symptoms and may be identified incidentally. Clinicians need to be aware that PVT can develop from various underlying conditions, including hypoplasia of the liver, and we recommend aggressive imaging studies to help detect the presence of PVT when encountering similar cases.

Prevalence and Impact of Social Frailty in Patients with Chronic Obstructive Pulmonary Disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) are more inclined to have a high level of social vulnerability due to their physical and psychological burden. However, to date, there have been no study on social frailty in patients with COPD. This study aimed to investigate the prevalence, characteristics, and impact of social frailty in patients with COPD. Methods: Social frailty was assessed using five items in a questionnaire. A patient was diagnosed with social frailty if responses to two or more items were positive. Four hundred and five patients with COPD were assessed for social frailty, dyspnea, and appetite. We also prospectively examined the number of acute exacerbation and unexpected hospitalization for 1 year. Results: Thirty-six percent of patients with COPD had social frailty. They had reduced appetite and more severe dyspnea [Simplified Nutritional Appetite Questionnaire score: odds ratio (OR) 0.81, 95% confidence interval (CI) 0.69‒0.95, p < 0.01; modified Medical Research Council score: OR 1.42, 95% CI 1.05‒1.93, P = 0.02] than patients without social frailty. Social frailty was not a risk factor for moderate acute exacerbation of COPD but a risk factor for severe acute exacerbation and all-cause unexpected hospitalization (severe acute exacerbation: ß, standardized regression coefficient: 0.13, 95% CI 0.01‒0.25, P = 0.04, unexpected hospitalization: ß 0.17, 95% CI 0.05‒0.29, P = 0.01). Conclusion: The prevalence of social frailty is 36%; however, social frailty has a marked clinical impact in patients with COPD.

Characteristics of and reasons for patients with chronic obstructive pulmonary disease to continue smoking, quit smoking, and switch to heated tobacco products.

INTRODUCTION: Smoking is the leading cause of chronic obstructive pulmonary disease (COPD), and smoking cessation is the most effective treatment for patients with COPD. However, few studies have investigated the continuation/cessation of smoking and heated tobacco products (HTP) in patients with COPD. The objective of this study was to examine the characteristics of patients with COPD, those who are current smokers and those who switched from cigarettes to HTP, and to examine the reason for the continuation or cessation of smoking. METHODS: This multicenter, cross-sectional study included 411 outpatients with COPD. Data for this study were part of a study conducted for a comprehensive evaluation of the smoking status and clinical factors in patients with COPD and their families. RESULTS: Logistic regression analysis revealed that a younger age, longer duration of smoking, fewer daily cigarettes, and lower modified Medical Research Council (mMRC) dyspnea score, and a lower Simplified Nutritional Appetite Questionnaire (SNAQ) score for appetite, were characteristics of current smokers (age OR=0.94; duration of smoking OR=1.07; number of cigarettes per day OR=0.94; mMRC OR=0.68; SNAQ OR=0.83; p<0.05). The logistic regression analysis model showed that a younger age and higher education level were associated with the use of HTP (age OR=0.83; higher education level OR=4.63; p<0.05). Many of the current smokers displayed smoking behaviors that are not guaranteed to be safe, such as reducing smoking or switching to lighter cigarettes or HTP. CONCLUSIONS: Patients with COPD who continue smoking tended to have low appetite as well as smoking behaviors that are not guaranteed to be safe. Physicians should provide appropriate guidance to these patients on smoking cessation.

Investigating Patient and Family Satisfaction with the Respiratory Status in Patients with Chronic Obstructive Pulmonary Disease.

The current chronic obstructive pulmonary disease (COPD) management aims to improve the patients' quality of life and healthy life expectancy; however, few studies have evaluated the level of satisfaction with the patients' current respiratory status in COPD patients and their families. This study aimed to examine the level of patient and family satisfaction with the patients' current respiratory status and to identify the clinical factors closely linked to dissatisfaction.This multicenter, cross-sectional study included 454 outpatients with COPD and 296 family members. Patients and families were allocated to the satisfied and dissatisfied groups based on their satisfaction with the patients' current respiratory status. Patients' health status, dyspnoea, appetite, respiratory function, and mood disorders were assessed.Among the participants of this study, 67% of patients and 60% of their families were dissatisfied with the patients' current respiratory status. The COPD assessment test (CAT) was the most sensitive marker of dissatisfaction compared to other clinical factors (p < 0.01). The statistical cut-off value of CAT for predicting patient dissatisfaction was 11. CAT reflected patient dissatisfaction independent of age, sex, dyspnoea, appetite, mood disorders, body mass index, and respiratory function (odds ratio: CAT; 1.12 (1.07-1.19): p < 0.01).Many patients and families are dissatisfied with the patients' respiratory status, and the patients' CAT score is useful to predict dissatisfaction. Our findings are consistent with the Global Initiative for Chronic Obstructive Lung Disease indicating that treatment should be enhanced in patients with a CAT score ≥10. Furthermore, treatment strategies targeting CAT may contribute to an improved patient satisfaction.

Activated protein C attenuates leukocyte elastase-induced lung injury in mice.

Leukocyte elastase (LE), a neutrophil serine protease, is known to cause alveolar wall destruction and alveolar hemorrhage in the lung, but recent evidence suggests that it may also produce a significant inflammatory response. The purpose of the current study was to (1) examine the relationship between LE-induced lung injury and specific markers of inflammation and cytokine/chemokine, and to (2) determine the potential of activated protein C (APC), a potent immunomodulator, to block the inflammatory response to LE. We treated the C57BL/6 mice with LE (10 U/kg, i.t.) and assessed the lung inflammation over 72 h. Total cells, total protein, and neutrophils were increased and peaked at 16 h in bronchial alveolar lavage fluid. Macrophages were also increased and peaked at 24 h. Administration of LE up-regulated the synthesis of proinflammatory cytokines, IL-1beta and IL-6, chemokines, keratinocyte-derived chemokine, and macrophage inflammatory protein 2 in bronchial alveolar lavage fluid, and their peaks were at 6 h. Furthermore, the mice were treated with APC at 0.2, 2.0, and 10 mg/kg (i.v.) after instillation of LE. Therapeutic treatment of APC at 2.0 and 10 mg/kg significantly attenuated the increases in all these parameters. Lung histology revealed that, in addition to inflammation, alveolar hemorrhage and alveolar wall destruction induced by LE were also attenuated by APC. Finally, the expression of tissue plasminogen activator and plasminogen activator inhibitor in whole lung of mice exposed to LE, detected by means of reverse-transcriptase-polymerase chain reaction, were not influenced by the treatment with APC. These data demonstrate that intratracheal administration of LE to mice causes a transient inflammatory response, and APC can play a protective role against LE-induced lung injury.

Silent brain infarction and platelet activation in obstructive sleep apnea.

RATIONALE: Silent brain infarction (SBI) and increased levels of soluble CD40 ligand (sCD40L) and soluble P-selectin (sP-selectin) are associated with an increased risk of cerebrovascular disease. OBJECTIVES: The aim of this study was to evaluate whether SBI and serum levels of sCD40L and sP-selectin are increased in patients with obstructive sleep apnea (OSA). METHODS: SBI was studied by brain magnetic resonance images in 50 male patients with OSA and 15 obese male control subjects who were free of comorbidities. In addition, the effects of 3 months of treatment with nasal continuous positive airway pressure (nCPAP) on serum parameters were studied in 24 patients with moderate to severe OSA. MEASUREMENTS AND MAIN RESULTS: The percentage of SBI in patients with moderate to severe OSA (25.0%) was higher than that of obese control subjects (6.7%) or patients with mild OSA (7.7%). Serum levels of sCD40L and sP-selectin were significantly higher in patients with moderate to severe OSA than in obese control subjects (p < 0.05) or patients with mild OSA (p < 0.05). In addition, nCPAP significantly decreased serum levels of sCD40L (p < 0.03) and sP-selectin (p < 0.01) in patients with moderate to severe OSA. CONCLUSIONS: These results suggest that serum levels of sCD40L and sP-selectin are elevated and SBI is more common in patients with moderate to severe OSA, leading to elevated cerebrovascular morbidity. Moreover, nCPAP may be useful for decreasing risk in patients with moderate to severe OSA.

Effect of fluvastatin on apoptosis in human CD4+ T cells.

Statins are lipid-lowering agents with pleiotropic effects. We investigated the apoptotic effects of fluvastatin on peripheral CD4+ T cells from healthy subjects. Fluvastatin induced apoptosis in resting CD4+ T cells but not in CD4+ T cells strongly activated with a high concentration of PMA plus ionomycin (PMA/I) analyzed with annexin V and propidium iodide staining. However, CD4+ T cells activated with a low concentration of PMA/I or with anti-CD3 antibodies were apoptotic after treatment with fluvastatin. Activities of caspases-8, -9, and -3 were increased in resting CD4+ T cells treated with fluvastatin (10 microM). In strongly activated CD4+ T cells, fluvastatin inhibited the activation of caspase-8 induced by PMA/I and increased caspase-9 activity. The caspase-3 activity did not differ between untreated and fluvastatin-treated strongly activated CD4+ T cells. Treatment with fluvastatin (10 microM) enhanced cytochrome c release and increased the Bax/Bcl-2 ratio in both resting and strongly activated CD4+ T cells. Although the in vitro concentration of fluvastatin used in this study is higher than in vivo, other factors may sensitize apoptotic cell death of CD4+ T cells in vivo. In conclusion, fluvastatin induces apoptosis in resting T cells but not in strongly activated T cells, a difference that might be due to the interaction between caspase-8 and caspase-9.

Increased carotid intima-media thickness and serum inflammatory markers in obstructive sleep apnea.

Increased carotid intima-media thickness (IMT) and increased serum levels of inflammatory markers, such as C-reactive protein (CRP), interleukin (IL)-6, and IL-18, are associated with an increased risk of cardiovascular and cerebrovascular diseases. The aim of this study was to evaluate whether carotid IMT, a useful marker for early atherosclerosis, is associated with these inflammatory markers in patients with obstructive sleep apnea (OSA). Carotid IMT was investigated with ultrasonography in 36 patients with OSA and 16 obese control subjects. Serum levels of CRP, IL-6, and IL-18 were measured at 5:00 A.M. Carotid IMT (p < 0.001) and serum levels of CRP (p < 0.003), IL-6 (p < 0.005), and IL-18 (p < 0.03) of patients with OSA were significantly higher than those of obese control subjects. Carotid IMT was significantly correlated with serum levels of CRP (r = 0.61, p = 0.0001), IL-6 (r = 0.41, p = 0.01), and IL-18 (r = 0.45, p = 0.005), duration of OSA-related hypoxia (r = 0.60, p = 0.0001), and severity of OSA (r = 0.50, p = 0.002). In addition, the primary factor influencing carotid IMT was duration of hypoxia during total sleep time (p = 0.036). These results suggest that OSA-related hypoxia and systemic inflammation might be associated with the progression of atherosclerosis and thus might increase the risks of cardiovascular and cerebrovascular morbidity in patients with OSA.

Interleukin-17F induces pulmonary neutrophilia and amplifies antigen-induced allergic response.

Interleukin (IL)-17F is a recently described human cytokine belonging to the IL-17 gene family, but its in vivo function remains to be determined. To this end, a full-length mouse IL-17F cDNA sequence with a 483-bp coding region sequence was first identified. Pulmonary gene transfer of an IL-17F expression construct (pcDNAmIL-17F) in mice was used to investigate its regulatory role. The results showed first that a significant increase in the number of neutrophils was seen in the bronchoalveolar lavage fluids of IL-17F-transduced mice, concomitant with increased expression of genes encoding C-X-C chemokines and inflammatory cytokines when compared with mock and phosphate-buffered saline control animals. Mucosal transfer of the IL-17F gene in ovalbumin (OVA)-sensitized mice before antigen (Ag) challenge enhanced the levels of Ag-induced pulmonary neutrophilia, but not eosinophilia, goblet cell hyperplasia, and mucin gene expression. However, no significant change in the levels of Th2 cytokine expression was noted. A significant enhancement of ventilatory timing in response to inhaled methacholine was also seen in IL-17F-transduced, Ag-sensitized mice, whereas a small but significant increase was found in IL-17F-transduced, naive mice. These results suggest a role for IL-17F in the induction of neutrophilia in the lungs and in the exacerbation of Ag-induced pulmonary inflammation.

IL-17 cytokine family.

A new family of cytokines, IL-17, has recently been defined that reveals a distinct ligand-receptor signaling system. Functional studies have provided evidence for its importance in the regulation of immune responses. Notably, 3 members, IL-17A, IL-17E (IL-25), and IL-17F, have been best characterized both in vitro and in vivo , and have been shown to be proinflammatory in nature. This proinflammatory activity is exemplified by their involvement in pulmonary inflammatory responses, in which both IL-17A and IL-17F are involved in the recruitment of neutrophils, and IL-17E is able to induce T H 2 cytokine production and eosinophilia. Although the elucidation of a detailed mechanism of action continues to be an active area of research, the potent inflammatory activity and its association with various human disease states suggest this new cytokine family as an important contributor to the pathophysiology of human disease conditions, in particular the pulmonary diseases.

Allergen rush immunotherapy increases interleukin (IL)-12 production and IL-12 receptor beta2 chain expression in patients with allergic asthma.

Interleukin (IL)-12 production and IL-12 receptor (IL-12R) beta2 chain expression were investigated in patients with allergic asthma successfully treated with rush immunotherapy (RIT) and control patients with mild allergic asthma. Peripheral blood mononuclear cells (PBMCs) were stimulated with Dermatophagoides farinae (Der f), and production of cytokines was measured. Furthermore, the effects of cytokines on IL-12R beta2 chain expression on CD4(+) T cells were investigated. Production by PBMCs of IL-12 and IFN-gamma was significantly higher and production of IL-4 was significantly lower after stimulation with Der f allergen in RIT-treated patients than in control patients. Significant increases in the expression of IL-12R beta2 chain before and after stimulation of CD4(+) T cells with IL-12 or IFN-gamma were observed in RIT-treated patients compared with that in control patients. Allergen RIT increases IL-12 production and IL-12R beta2 chain expression and thus may convert cytokine production from Th2 to Th1 or Th0 type in allergic asthma.

Elevated levels of C-reactive protein and interleukin-6 in patients with obstructive sleep apnea syndrome are decreased by nasal continuous positive airway pressure.

BACKGROUND: C-reactive protein (CRP) and interleukin (IL)-6 are important risk factors for atherosclerosis and coronary heart disease. In the present study, we examined serum levels of CRP and IL-6, IL-6 production by monocytes, and the effect of nasal continuous positive airway pressure (nCPAP) in patients with obstructive sleep apnea syndrome (OSAS). METHODS AND RESULTS: After polysomnography, venous blood was collected at 5 AM from 30 patients with OSAS and 14 obese control subjects. Serum levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes were investigated. In addition, the effects of 1 month of nCPAP were studied in patients with moderate to severe OSAS. Levels of CRP and IL-6 were significantly higher in patients with OSAS than in obese control subjects (CRP P<0.001, IL-6 P<0.05). IL-6 production by monocytes was also higher in patients with OSAS than in obese control subjects (P<0.01). In patients with OSAS, the primary factors influencing levels of CRP were severity of OSAS and body mass index and those influencing levels of IL-6 were body mass index and nocturnal hypoxia. nCPAP significantly decreased levels of both CRP (P<0.0001) and IL-6 (P<0.001) and spontaneous IL-6 production by monocytes (P<0.01). CONCLUSIONS: Levels of CRP and IL-6 and spontaneous production of IL-6 by monocytes are elevated in patients with OSAS but are decreased by nCPAP. Therefore, OSAS is associated with increased risks for cardiovascular morbidity and mortality, and nCPAP may be useful for decreasing these risks.

[Japanese cedar pollinosis is a risk factor for bronchial asthma in Japanese adult asthmatics].

It is well known that allergic rhinitis and asthma often coexist in the same patients. Here, we investigated the influence of Japanese cedar pollinosis on the exacerbation of asthma investigated by questionnaire, daily asthma diary, and peak expiratory flow (PEF) monitoring. Furthermore, airway responsiveness to histamine before pollen season was also investigated in some patients. 333 adult patients with asthma were enrolled into the study and 116 patients (34.8%) were suffering from Japanese cedar pollinosis diagnosed by the presence of nasal allergic symptoms during pollen season and high titer of Japanese cedar-specific IgE antibody. Exacerbation of asthma symptoms, including wheezing, dyspnea, cough, and sputum, was detected in 41 of 116 patients (35.3%) during pollen season. Decrease in morning PEF more than 10% compared with the baseline values before pollen season was observed in 13 of 41 patients (11.2% of total asthmatic patients who complicated with Japanese cedar pollinosis). No significant differences in airway responsiveness to histamine and the titer of Japanese cedar-specific IgE antibodies before pollen season were observed between the patients whose asthma exacerbated and the patients whose asthma was not exacerbated. These results suggest that Japanese cedar pollinosis is one of risk factors for asthma in Japanese adult patients with asthma.

Inhibitory effect of lidocaine on T cells from patients with allergic asthma.

BACKGROUND: Nebulized lidocaine enables dosages of oral corticosteroids to be tapered in the treatment of severe asthma. OBJECTIVE: We sought to investigate the effect of lidocaine on T cells from patients with allergic asthma. METHODS: PBMCs and CD4(+) T cells were isolated from 6 patients with asthma and house dust mite allergy. PBMCs were cultured with lidocaine for up to 7 days and then stained with propidium iodide to evaluate the involvement of apoptosis. In addition, the viability of CD4(+) T cells when cultured with lidocaine was investigated. Effects of lidocaine on proliferative response, mRNA expression, and protein production of IL-5 and IFN-gamma by PBMCs were investigated after stimulation with Dermatophagoides farinae, purified protein derivative, and phorbol 12-myristate 13-acetate plus calcium ionophore. The effects of lidocaine on the proliferative response of steroid-insensitive PBMCs from 6 nonallergic donors induced by preculture with IL-2 and IL-4 were also investigated. RESULTS: No significant increase in the staining of PBMCs with propidium iodide was observed in the presence of 100 micromol/L lidocaine. The viability of CD4(+) T cells was not significantly affected by culture with lidocaine at this concentration. However, lidocaine inhibited, in a dose-dependent manner, the proliferative response and mRNA expression and protein production of IL-5 and IFN-gamma of PBMCs stimulated with D farinae, purified protein derivatives, or phorbol 12-myristate 13-acetate plus calcium ionophore. Preincubation of PBMCs with IL-2 and IL-4 significantly decreased the inhibitory effects of both corticosteroids and lidocaine compared with that after preincubation with medium alone. CONCLUSION: Lidocaine has immunoregulatory effects on T cells. Therefore, lidocaine might be studied as an anti-inflammatory agent in the treatment of severe steroid-dependent asthma.