Efficacy of tezepelumab against uncontrolled severe non-type 2 asthma refractory to bronchial thermoplasty, benralizumab, dupilumab and mepolizumab.

Severe asthma affects approximately 5%-10% of patients with asthma. Herein, we describe a case of non-type 2 asthma that progressively worsened over the years. An 80-year-old woman was diagnosed with asthma 11 years back. She experienced repeated exacerbations requiring treatment with systemic corticosteroid despite therapy with medications including high-dose inhaled corticosteroids/long-acting beta-agonists plus long-acting muscarinic antagonist. The patient presented with non-eosinophilic asthma. Therefore, the patient was initially treated with bronchial thermoplasty, which was effective for 1 year only. Treatment with bronchial thermoplasty, benralizumab, dupilumab, and mepolizumab was ineffective. The fourth treatment, which included tezepelumab, was initiated. The patient's symptoms and quality of life improved significantly. This is the first case of a patient who did not respond to sequential bronchial thermoplasty, benralizumab, dupilumab, and mepolizumab but who presented with good clinical response to tezepelumab. Therefore, tezepelumab may be useful for patients with non-type 2 asthma.

Antiviral Effect of Candies Containing Persimmon-Derived Tannin against SARS-CoV-2 Delta Strain.

Inactivation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the mouth has the potential to reduce the spread of coronavirus disease 2019 (COVID-19), due to the virus being readily transmitted by dispersed saliva. Persimmon-derived tannin has strong antioxidant and antimicrobial activity owing to its strong adhesion to proteins, and it also exhibited antiviral effects against non-variant and Alpha-variant SARS-CoV-2 in our previous study. In this study, we first demonstrated the antiviral effects of persimmon-derived tannin against the Delta variant of SARS-CoV-2 in vitro via the plaque assay method. We then examined the effects of candy containing persimmon-derived tannin. Remarkably, the saliva samples provided by healthy volunteers while they were eating tannin-containing candy showed that the virus titers of the SARS-CoV-2 Delta variant were suppressed. In addition, we found that the SARS-CoV-2 viral load in saliva from patients with COVID-19 collected immediately after they had eaten the tannin-containing candy was below the level of detection via PCR for SARS-CoV-2. These data suggest that adding persimmon-derived tannin to candy and holding such candy in the mouth is an effective method for inactivating SARS-CoV-2 in saliva, and the application of this approach shows potential for inhibiting the transmission of COVID-19.

Difficulties in Differentiating Osteosclerosis in Patients With Multifocal Micronodular Pneumocyte Hyperplasia and Cancer.

A 52-year-old woman with multifocal micronodular pneumocyte hyperplasia in bilateral lungs and multiple sclerotic bone lesions (SBLs) visited our hospital. Tuberous sclerosis complex (TSC) was suspected but did not meet the diagnostic criteria. Ten years later, at age 62, the patient developed ureteral cancer. Cisplatin-containing chemotherapy ameliorated ureteral tumor, concomitant with exacerbation of SBLs. It was difficult to distinguish whether the exacerbation of SBLs was due to exacerbation of TSC or bone metastasis of cancer. The administration of cisplatin made the diagnosis even more difficult because its molecular biological effects can exacerbate the complications of TSC.

Classifications of moderate to severe asthma phenotypes in Japan and analysis of serum biomarkers: A Nationwide Cohort Study in Japan (NHOM Asthma Study).

BACKGROUND: Asthma is a heterogeneous disease, and phenotyping can facilitate understanding of disease pathogenesis and direct appropriate asthma treatment. This nationwide cohort study aimed to phenotype asthma patients in Japan and identify potential biomarkers to classify the phenotypes. METHODS: Adult asthma patients (n = 1925) from 27 national hospitals in Japan were enrolled and divided into Global Initiative for Asthma (GINA) steps 4 or 5 (GINA 4, 5) and GINA Steps 1, 2, or 3 (GINA 1-3) for therapy. Clinical data and questionnaires were collected. Biomarker levels among GINA 4, 5 patients were measured. Ward's minimum variance hierarchical clustering method and tree analysis were performed for phenotyping. Analysis of variance, the Kruskal-Wallis, and chi-square tests were used to compare cluster differences. RESULTS: The following five clusters were identified: 1) late-onset, old, less-atopic; 2) late-onset, old, eosinophilic, low FEV1; 3) early-onset, long-duration, atopic, poorly controlled; 4) early-onset, young, female-dominant, atopic; and 5) female-dominant, T1/T2-mixed, most severe. Age of onset, disease duration, blood eosinophils and neutrophils, asthma control questionnaire Sum 6, number of controllers, FEV1, body mass index (BMI), and hypertension were the phenotype-classifying variables determined by tree analysis that assigned 79.5% to the appropriate cluster. Among the cytokines measured, IL-1RA, YKL40/CHI3L1, IP-10/CXCL10, RANTES/CCL5, and TIMP-1 were useful biomarkers for classifying GINA 4, 5 phenotypes. CONCLUSIONS: Five distinct phenotypes were identified for moderate to severe asthma and may be classified using clinical and molecular variables (Registered in UMIN-CTR; UMIN000027776.).

Randomized double-blind placebo-controlled multicenter trial for the effects of a polyherbal remedy, Yokukansan (YiganSan), in smokers with depressive tendencies.

BACKGROUND: Smoking and depression are closely related and form a vicious cycle. Yokukansan (YiganSan) is a polyherbal remedy that has the effect of calming neuropsychiatric symptoms such as anger and irritation. To examine the efficacy of Yokukansan during smoking cessation (SC) therapy in smokers with depressive tendencies but without major depressive disorders requiring pharmacotherapy. METHODS: A multicenter, double-blind, randomized, placebo-controlled, parallel-group comparison trial was conducted between June 2016 and May 2020 at 12 centers of the National Hospital Organization, Japan. This trial targeted smokers who first visited the SC outpatient clinics, did not receive any pharmacological treatment at the psychiatric or psychosomatic department, and scored 39 or more on the self-rating depression scale (SDS). Participants (n = 198) were randomly assigned to either the Yokukansan or placebo groups. The trial drug was initiated with the start of the SC treatment and continued for 12 weeks. The primary outcome was the high success rate of the SC treatment, and the secondary outcomes included changes in scores of the SDS and the Profile of Mood States (POMS) instrument. RESULTS: The success rate of the SC treatment was similar between the placebo (63%) and Yokukansan (67%) groups (P = .649). The SDS scores (placebo: mean difference [MD] = -3.5, 95% confidence interval [CI][-5.8, -1.2], d = 0.42; Yokukansan: MD = -4.6, 95%CI[-6.8, -2.3], d = 0.55), and the "tension-anxiety" POMS-subscale scores (placebo: MD = -1.6, 95%CI[-2.5, -0.7], d = 0.52; Yokukansan: MD = -1.6, 95%CI[-2.9, -0.3], d = 0.36) showed significant improvement in both groups after the SC treatment. However, "depression-dejection" improved in the Yokukansan group (MD = -1.9, 95%CI[-3.1, -0.7], d = 0.44) but not in the placebo group (MD = -0.1, 95%CI[-1.0, 0.7], d = 0.04). Significant improvement in "fatigue" was noted in the Yokukansan group (MD = -2.1, 95%CI[-3.4, -0.9], d = 0.47) but not in the placebo group (MD = -0.5, 95%CI[-1.8, 0.8], d = 0.11). The time × group interaction on the improvement in "depression-dejection" was significant (P = .019). CONCLUSIONS: Yokukansan does not increase the SC treatment's success rate but has additional positive effects on the psychological states due to the SC treatment in smokers with depressive tendencies but without apparent mental disorders. TRIAL REGISTRATION: ID: UMIN000027036. Retrospectively registered at UMIN on April 18, 2017.

A case of diffuse aspiration bronchiolitis due to oesophageal stenosis after radiation therapy.

A 66-year-old woman was hospitalized for recurrent pneumonia twice in 1 year. After treatment for pneumonia, chronic coughing, sputum and low-grade fever continued, so she was referred and admitted to our hospital for investigation. Chest computed tomography revealed a lung infiltrative shadow and diffuse centrilobular micronodules. Histological findings from transbronchial lung biopsy showed chronic inflammation and giant cells in the bronchiole. These findings were compatible with diffuse aspiration bronchiolitis (DAB), which is characterized by chronic inflammation of the bronchioles caused by recurrent aspiration of foreign bodies. Oesophagogastroduodenoscopy revealed stenosis of the oesophageal entrance, which was thought to be caused by radiation therapy for hypopharyngeal cancer 20 years before. Antibiotic treatment ameliorated the centrilobular nodule shadow. After discharge, there was no recurrence. This is the first case report of DAB resulting from oesophageal stenosis associated with hypopharyngeal cancer and will serve as an educational case.

The impact of obstructive sleep apnea and nasal CPAP on circulating adiponectin levels.

PURPOSE: Although obstructive sleep apnea syndrome (OSAS) is known to be an important risk factor for cardiovascular diseases, the mechanism behind this association has not been fully elucidated. Transendothelial migration of monocytes mediated by adhesion molecules is a crucial step in the pathogenesis of atherosclerosis. We investigated the effect of hypoxic stress on plasma adiponectin and tumor necrosis factor-α (TNF-α) levels and whether adiponectin and TNF-α modulate adhesion molecules in patients with OSAS. METHODS: In 22 patients, plasma adiponectin and TNF-α levels and serum concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) were determined early in the morning after polysomnography and after nasal continuous positive airway pressure (nCPAP) treatment. RESULTS: Plasma adiponectin levels were inversely correlated with the apnea-hypopnea index (AHI) (r = -0.582, p < 0.005) and % time in SpO2 <90 % (r = -0.539, p < 0.01) but not with the body mass index (BMI). TNF-α levels were positively correlated with the AHI (r = 0.462, p < 0.05) and BMI (r = 0.452, p < 0.05). Serum sICAM-1 levels were inversely correlated with plasma adiponectin levels (r = -0.476, p < 0.05) but not with TNF-α levels. Although plasma TNF-α levels decreased after overnight nCPAP treatment (p < 0.05), plasma adiponectin levels increased after long-term nCPAP (3 months) treatment (p < 0.02) in ten patients. CONCLUSIONS: Our findings suggest that reduced adiponectin and elevated TNF-α levels in plasma are associated with OSAS-induced hypoxic stress. Decreased adiponectin levels are associated with sICAM-1 levels.

Distribution of bone mineral content is associated with body weight and exercise capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Although low bone mineral density is highly prevalent in patients with chronic obstructive pulmonary disease (COPD), the distribution of the reduced bone mass has not been fully elucidated. OBJECTIVES: To determine regional bone mass loss in patients with COPD and investigate whether the change in distribution may be associated with body weight loss and functional capacity. METHODS: Body mass index (BMI) was assessed, and height squared indices were derived for the bone mineral content index (BMCI) of the arms, legs and trunk by dual-energy X-ray absorptiometry in 45 male patients with COPD and 12 age- and sex-matched control subjects. Pulmonary function tests were performed, and maximal oxygen uptake (VO2max) was measured. RESULTS: The BMCI was lower in the total bone, legs and trunk of patients with COPD than in control subjects, although the BMCI in the arms was similar between the groups. BMI correlated significantly with the BMCI in all 3 segments. Bone mineral content (BMC) in the trunk, expressed as a percentage of total BMC (BMC trunk/total BMC), correlated significantly with BMI. The BMCI in the trunk was closely related with VO2max but not with airflow limitation. CONCLUSIONS: There was a regional difference in BMC reduction, but a predominant reduction of bone mass in the trunk was not associated with the severity of airflow limitation but rather with body weight loss and exercise intolerance. These data suggest that body weight loss and exercise intolerance are important risk factors for vertebral fracture in patients with COPD.

Pancreatic ß cell proliferation by intermittent hypoxia via up-regulation of Reg family genes and HGF gene.

AIMS: Although accumulating evidence suggests the associations between sleep apnea syndrome (SAS) and type 2 diabetes, the direct effect of intermittent hypoxia (IH) on pancreatic ß cell proliferation remains a missing piece of the puzzle. MAIN METHODS: Rat RINm5F ß cells, hamster HIT-T15 ß cells, and human 1.1B4 ß cells were exposed to normoxia (21% O2, 5% CO2, and balance N2), to sustained hypoxia (SH: 1% O2, 5% CO2, and balance N2), or to intermittent hypoxia (IH: 64 cycles of 5 min SH and 10 min normoxia) for 24 h. After the treatment, cellular proliferation and apoptosis were measured by WST-8 assay and TUNEL method, respectively. The expression of regenerating gene (Reg) family, interleukin (IL)-6, and hepatocyte growth factor (HGF) was determined by real-time RT-PCR. KEY FINDINGS: The cellular proliferation of HIT-T15, RINm5F and 1.1B4 cells by IH was significantly increased, whereas apoptosis of these cells was unchanged. Real-time RT-PCR revealed that the mRNA levels of Reg family genes, IL-6, a typical Reg family gene inducer, and HGF, an inhibitor of high-concentration of Reg protein-induced apoptosis, were increased in IH-treated cells. In addition, siRNAs against rat Reg family genes except for PAP I/Reg 2 attenuated IH-induced ß cell proliferation. SIGNIFICANCE: IH stress stimulates pancreatic ß cell to induce IL-6 gene expression. By the IL-6 stimulation, ß cells over-express Reg family genes as well as HGF gene. Reg family proteins stimulate ß cell proliferation and HGF inhibits apoptosis of ß cells. As a result, ß cell numbers are increased by IH.

Reduced larger von Willebrand factor multimers at dawn in OSA plasmas reflect severity of apnoeic episodes.

Plasma von Willebrand factor (VWF), produced in and released from vascular endothelial cells by various stimuli including hypoxia, induces platelet aggregation under high shear stress and plays dual pivotal roles in haemostasis and thrombosis within arterioles, which are regulated by the size of vWF multimers (VWFMs). Patients with obstructive sleep apnoea (OSA) have increased risk of thrombotic cardiovascular events, but the pathogenesis is unclear. We examined the relationship between VWF and OSA by measuring VWF antigen (VWF:Ag), VWFMs, VWF collagen binding activity (VWF:CB) and a disintegrin-like, metalloproteinase, and thrombospiondin type 1 motifs 13. A total of 58 OSA patients were enrolled. Blood samples were collected before sleep, after sleep, and after one night of nasal continuous positive airway pressure therapy. Based on VWFM analysis, OSA patients were classified into three groups; consistently normal VWFMs (group 1, n=29), increased high molecular weight (HMW)-VWFMs at 06:00 h (group 2, n=18), and decreased or absent HMW-VWFMs at 06:00 h (group 3, n=11). Patients in group 3 had significantly worse apnoea/hypopnoea index; VWF:CB followed a similar pattern. We observed a significant decrease in platelet count between 21:00 h and 06:00 h in OSA patients, potentially associated with reduced larger VWFMs together with decreased VWF:Ag levels. Severe OSA may contribute to an arterial pro-thrombotic state.

Attenuation of glucose-induced insulin secretion by intermittent hypoxia via down-regulation of CD38.

AIMS: Sleep apnea syndrome (SAS) is characterized by recurrent episodes of oxygen desaturation during sleep, the development of daytime sleepiness, and deterioration in the quality of life. Accumulating evidence suggests the association of intermittent hypoxia (IH), a hallmark of SAS, and type 2 diabetes independently on body mass index and waist circumference. In addition to insulin resistance, the progression to type 2 diabetes is dependent on the impairment of glucose-induced insulin secretion (GIS) from pancreatic ß-cells. However, the direct effects of IH on GIS are elusive. MAIN METHODS: HIT-T15 hamster ß-cells and isolated rat islets were exposed to 64 cycles/24 h of IH (5 min hypoxia/10 min normoxia) or normoxia for 24 h. Changes of GIS and gene expression in IH-treated ß-cells were analyzed by ELISA and real-time RT-PCR, respectively. KEY FINDINGS: After IH treatment, GIS both from IH-treated HIT-T15 cells and isolated rat islets were significantly attenuated. The level of insulin mRNA was unchanged by IH. The mRNA levels of glucose transporter 2 (Glut2), glucokinase (GK), sulfonylurea receptor1 (SUR1), and L-type Ca2+channel1.2 (Cav1.2) in IH-treated-islets were similar to those in normoxia-treated islets. In contrast, the mRNA level of CD38 in IH-treated islets was significantly lower than that in normoxia-treated islets. The reporter gene assay revealed that the transcription of CD38 was attenuated by IH, and the transfection of CD38 expression vector recovered the attenuation of GIS by IH. SIGNIFICANCE: These results indicate that IH stress directly attenuates GIS from ß-cells via the down-regulation of CD38.

Neurovascular decompression of the rostral ventrolateral medulla decreases blood pressure and sympathetic nerve activity in patients with refractory hypertension.

Recently, the authors experienced four patients who had refractory hypertension and neurovascular compression of the rostral ventrolateral medulla (RVLM). One of them, a 49-year-old woman, had undergone continuous intravenous drip injections of calcium channel blockers and ß-blockers for more than 3 years because of severe and refractory hypertension. The patients had undergone microvascular decompression (MVD) of the RVLM, and the changes in blood pressure (BP) and sympathetic nerve activities were recorded. In these patients, BP decreased to the normal range without any antihypertensive drugs 2 to 3 months after MVD. The tibial sympathetic nerve activities under resting and stress conditions significantly decreased, and plasma levels of norepinephrine, urinary levels of adrenaline, and plasma renin activity were also significantly decreased after MVD of RVLM. In some patients with refractory hypertension, arterial compression of the RVLM enhances sympathetic nerve activity and renin-angiotensin system to thereby increase BP. In these patients, the operative decompression of the RVLM could lower BP via restoration of sympathetic nerve activities and the renin-angiotensin system.

Early decrease in α-fetoprotein, but not des-γ-carboxy prothrombin, predicts sorafenib efficacy in patients with advanced hepatocellular carcinoma.

OBJECTIVES: The aim of this study was to investigate the relationships between early changes in the tumor markers α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP), and antitumor response in the early period following administration of sorafenib in patients with advanced hepatocellular carcinoma (HCC). METHODS: Forty-eight advanced HCC patients were evaluated. AFP and DCP were measured at baseline, and after 2 and 4 weeks, and the antitumor responses were evaluated according to the RECIST criteria 4 weeks after starting sorafenib therapy. The ratios of each tumor marker were compared by stratifying the patients into the partial response (PR) + stable disease (SD) group or the progressive disease (PD) group. RESULTS: Both 2 and 4 weeks after starting sorafenib therapy, the AFP ratio in the PR + SD group (n = 32) was significantly lower than in the PD group (n = 16; p = 0.002, p = 0.002). DCP was elevated in both the PR + SD group and the PD group 2 weeks and 4 weeks after starting sorafenib therapy. CONCLUSIONS: Evaluation of AFP ratios 2 and 4 weeks after starting sorafenib therapy may be useful for predicting antitumor response. On the other hand, early elevation of DCP does not necessarily suggest treatment failure by sorafenib, as DCP elevation can occur despite therapeutic efficacy.

Differences in breathing patterning during wakefulness in patients with mixed apnea-dominant vs obstructive-dominant sleep apnea.

BACKGROUND: Mixed apneas share both central and obstructive components and are often treated as if they are obstructive events. The hypothesis is that patients with obstructive sleep apnea syndrome (OSAS) who exhibit a majority of mixed apneas will differ in ventilatory control from those with predominantly obstructive apneas during wakefulness; moreover, this difference could affect nasal continuous positive airway pressure (CPAP) adherence. METHODS: In a retrospectively derived case-control study, 5 min of respiratory inductance plethysmography signals during wakefulness prior to sleep onset were extracted from a diagnostic polysomnogram in these groups: (1) mixed apnea-dominant OSAS (mix-OSAS) (n = 36), (2) obstructive apnea-dominant OSAS (pure-OSAS) (n = 20), (3) central apnea-dominant sleep apnea syndrome (pure-CSAS) (n = 6), and (4) control subjects (n = 10). Breathing patterning was compared between the groups using the coefficient of variation (CV) for breath-to-breath inspiration time (TI), expiration time (TE), TI + TE (Ttot), and tidal volume, and an information theory-based metric of signal pattern variability (sample entropy). Subsequent CPAP adherence over 12 months was determined in OSAS groups. RESULTS: Breath-to-breath CV parameters and sample entropy in the mix-OSAS group were significantly greater as compared with the pure-OSAS and control groups. In a subanalysis, CV and sample entropy were similar in the mix-OSAS and the pure-CSAS groups. CPAP adherence was significantly poorer in mix-OSAS compared with pure-OSAS. CONCLUSIONS: During wakefulness, both breath patterning and sample entropy in mix-OSAS are similar to pure-CSAS and more variable than in pure-OSAS. In addition, CPAP adherence was decreased in patients with mix-OSAS, which may be related to basic differences in respiratory control.

Production of inflammatory mediators by monocytes in patients with obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is known to be a risk factor of cardiovascular events. However, the precise mechanism linking the two has not been fully elucidated. OBJECTIVE: The aim of this study was to investigate the effect of hypoxic stress on the production of tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-9 (MMP-9) by monocytes. METHODS: Thirty-three OSAS patients and 13 healthy control subjects were enrolled. The OSAS patients were classified as mild-to-moderate (13) and severe (20). Venous blood samples were collected before and after sleep as well as after long-term nasal continuous positive airway pressure (CPAP) treatment for the purpose of isolation of monocytes. Peripheral blood monocytes were isolated using standard methods. Monocytes were cultured under lipopolysaccharide stimulation for 24 hours, and TNF-alpha, MCP-1, and MMP-9 in the culture supernatants were determined by ELISA. RESULTS: In severe patients, the TNF-alpha production by monocytes was significantly elevated as compared to that before sleep (p<0.01). In all OSAS patients, the TNF-alpha production after sleep was significantly correlated with AHI (p<0.01), ODI (p<0.01) and % time in SpO(2)<90% (p<0.05), and inversely correlated with the lowest SpO(2) (p<0.01). The production of MCP-1 and MMP-9 by monocytes was significantly elevated compared to that before sleep in severe patients (p<0.05). The production of these mediators by monocytes was significantly decreased after long-term nasal CPAP treatment (p<0.05). CONCLUSION: These results indicate that OSAS-induced hypoxic stress activates the production of inflammatory mediators by monocytes.

Nocturnal hypoxic stress activates invasive ability of monocytes in patients with obstructive sleep apnoea syndrome.

BACKGROUND AND OBJECTIVE: Obstructive sleep apnoea syndrome (OSAS) is known to be a risk factor for cardiovascular events. However, the precise mechanism has not been fully elucidated. OSAS-induced hypoxic stress may promote the production of inflammatory cytokines and chemokines by monocytes, which has a crucial role in the development of atherosclerosis. In addition, adhesion to the vascular endothelium and transendothelial migration of monocytes are considered to induce atherosclerosis. The aim of this study was to investigate the effects of hypoxic stress on the invasive ability of monocytes in OSAS. METHODS: Twenty-one male patients with OSAS and 17 healthy male control subjects, who were matched for age and BMI, were enrolled. Venous blood samples were collected before and after sleep, and also after CPAP titration, for the purpose of monocyte isolation. The invasive ability of monocytes was evaluated by counting the number of invading cells using a BD BioCoat Matrigel Invasion Chamber. RESULTS: The number of cells, which represents the invasive ability of monocytes, was significantly higher in patients with OSAS compared with control subjects, in the early morning (P < 0.001). In patients with OSAS, invasive ability in the early morning after sleep was significantly elevated as compared with that before sleep (P < 0.001), and was positively correlated with the oxygen desaturation index (P < 0.05). CPAP titration led to a decrease in the invasive ability (P < 0.001). CONCLUSIONS: These results indicate that OSAS-induced hypoxic stress activates the invasive ability of monocytes, and that the occurrence of this phenomenon during sleep may contribute to the development of atherosclerosis in OSAS.

Association between polymorphism of the AGTR1 and cardiovascular events in a Japanese general sample (The Shigaraki Study).

We examined whether the A1166C polymorphism of the angiotensin II type I receptor gene (AGTR1) affects cardiovascular event occurrence in a Japanese prospective cohort study. The 2212 participants who gave informed consent for genetic analysis were enrolled in this study (the Shigaraki Study). The average observation period was 1954 days. Cardiovascular events occurred in 37 individuals (1.7%). The independent factors which specified cardiovascular events were age (hazard ratio (HR)=1.13; 95% confidence interval (CI): 1.10-1.16; p<0.0001) and sex (HR=2.18; 95%CI: 1.23-3.85; p=0.007). However, the A1166C polymorphism of AGTR1 was not a predictive factor for cardiovascular events (HR=1.11; 95%CI: 0.61-2.02; p=0.731).

Perforated mitral valve aneurysm associated with Libman-Sacks endocarditis.

The perforation of a mitral valve aneurysm is a rare disease which induces acute mitral regurgitation and is usually induced by infective endocarditis; however, in this case report, acute heart failure was caused by a perforated mitral valve aneurysm that was speculated to be due to Libman-Sacks endocarditis with systemic lupus erythematosis and secondary anti-phospholipid syndrome. Mitral valve plasty was performed and thereafter heart failure improved.

The factors contributing to whether or not hypertensive patients bring their home blood pressure record to the outpatient clinic.

OBJECTIVE: We investigated the factors contributing to whether or not hypertensive patients brought their home blood pressure records to the outpatient clinic. METHOD: We studied 325 hypertensive patients [169 men (66.3+/-11.4 years old) and 156 women (68.1+/-11.2 years old)] who had received medical treatment for hypertension in our outpatient clinic from June to August 2006. RESULTS: Of the 325 patients studied, 206 (63.4%, 101 men, 105 women) brought their home blood pressure records to our outpatient clinic. Logistic analysis showed age [odds ratio (OR) =0.95; 95% confidence interval (CI): 0.93-0.98; p=0.0002], systolic blood pressure in outpatient clinic (OR=1.02; 95% CI: 1.00-1.04; p=0.0488) and the number of medicines prescribed (OR=1.94; 95% CI: 1.37-2.75; p=0.0002) were independent factors contributing to whether or not hypertensive patients bring along their home blood pressure records to the outpatient clinic. CONCLUSION: The contributing factors determining whether the patients bring their home blood pressure records to the outpatient clinic were: younger age, higher systolic blood pressure in the outpatient clinic, and a higher number of antihypertensive drugs. In conclusion, our results suggest that physicians should further motivate older patients, with well-controlled blood pressure in the outpatient clinic, to bring their home blood pressure records to the outpatient clinic.