P2X7 receptor blockade reduces pyroptotic inflammation and promotes phagocytosis in Vibrio vulnificus infection.

Vibrio vulnificus, a gram-negative bacterium, causes serious wound infections and septicemia. Once it develops into early phase sepsis, hyperinflammatory immune responses result in poor prognosis in patients. The present study aimed to examine the possible underlying pathogenic mechanism and explore potential agents that could protect against V. vulnificus cytotoxicity. Here, we report that infection of mouse macrophages with V. vulnificus triggers antiphagocytic effects and pyroptotic inflammation via ATP-mediated purinergic P2X7 receptor (P2X7R) signaling. V. vulnificus promoted P2X7-dependent nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 translocation, modulating the expression of the inflammasome sensor NLR family pyrin domain containing 3 (NLRP3), adaptor apoptosis-associated speck-like protein containing a card (ASC), and pyroptotic protein gasdermin D (GSDMD) in mouse macrophages. V. vulnificus induced the NLRP3/caspase-1 inflammasome signaling complex expression that drives GSDMD transmembrane pore formation and secretion of interleukin (IL)-1ß, IL-18, and macrophage inflammatory protein-2 (MIP-2). This effect was blocked by P2X7R antagonists, indicating that the P2X7R mediates GSDMD-related pyroptotic inflammation in macrophages through the NF-κB/NLRP3/caspase-1 signaling pathway. Furthermore, blockade of P2X7R reduced V. vulnificus-colony-forming units in the spleen, immune cell infiltration into the skin and lung tissues, and serum concentrations of IL-1ß, IL-18, and MIP-2 in mice. These results indicate that P2X7R plays a vital role in mediating phagocytosis by macrophages and pyroptotic inflammation during V. vulnificus infection and provides new opportunities for therapeutic intervention in bacterial infections.

MMP-10 from M1 macrophages promotes pulmonary vascular remodeling and pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by muscularized pulmonary blood vessels, leading to right heart hypertrophy and cardiac failure. However, state-of-the-art therapeutics fail to target the ongoing remodeling process. Here, this study shows that matrix metalloproteinases (MMP)-1 and MMP-10 levels are increased in the medial layer of vessel wall, serum, and M1-polarized macrophages from patients with PAH and the lungs of monocrotaline- and hypoxia-induced PAH rodent models. MMP-10 regulates the malignant phenotype of pulmonary artery smooth muscle cells (PASMCs). The overexpression of active MMP-10 promotes PASMC proliferation and migration via upregulation of cyclin D1 and proliferating cell nuclear antigen, suggesting that MMP-10 produced by infiltrating macrophages contributes to vascular remodeling. Furthermore, inhibition of STAT1 inhibits hypoxia-induced MMP-10 but not MMP-1 expression in M1-polarized macrophages from patients with PAH. In conclusion, circulating MMP-10 could be used as a potential targeted therapy for PAH.

Combination therapy of iPSC-derived conditioned medium with ceftriaxone alleviates bacteria-induced lung injury by targeting the NLRP3 inflammasome.

The lung is the first and most frequent organ to fail among sepsis patients. The mortality rate of sepsis-related acute lung injury (ALI) is high. Despite appropriate antimicrobial therapy, no treatment strategies are available for sepsis-induced ALI. Stem cell-mediated paracrine signaling is a potential treatment method for various diseases. This study aimed to examine the effects of induced pluripotent stem cell-derived conditioned medium (iPSC-CM) combined with antibiotics on ALI in a rat model of Escherichia coli-induced sepsis. Rats were administered either iPSC-CM or the vehicle (saline) with antibiotics (ceftriaxone). After 72 h, liquid biopsy, bronchoalveolar lavage fluid (BALF), and tissues were harvested for analysis. Survival rates were observed for up to 3 days. Furthermore, we examined the effects of iPSC-CM on cytokine production, metalloproteinase 9 (MMP-9) expression, and NLRP3-ASC interaction in RAW264.7 cells stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ). Combined treatment of iPSC-CM with antibiotics significantly improved survival in E. coli-infected rats (p = 0.0006). iPSC-CM ameliorated E. coli-induced infiltration of macrophages, reducing the number of cells in BALF, and suppressing interleukin (IL)-1ß, MIP-2, IL-6, and MMP-9 messenger RNA in lung sections. iPSC-CM treatment attenuated NLRP3 expression and inhibited NLRP3 inflammasome activation by disrupting NLRP3-mediated ASC complex formation in LPS/IFN-γ-primed RAW264.7 cells. This study reveals the mechanisms underlying iPSC-CM-conferred anti-inflammatory activity in ALI through the attenuation of macrophage recruitment to the lung, thus inactivating NLRP3 inflammasomes in macrophages. iPSC-CM therapy may be a useful adjuvant treatment to reduce sepsis-related mortality by ameliorating ALI.

Dual trajectories of loneliness and depression and their baseline correlates over a 14-year follow-up period in older adults: Results from a nationally representative sample in Taiwan.

AIMS: To explore the codevelopment between loneliness and depression in older adults, and to identify its potential baseline individual, family and extrafamilial correlates. BACKGROUND: The number of older adults around the world has steadily increased over the last decades. Later life is a particularly vulnerable life stage due to multiple unfavourable conditions, and mental health in this stage appears to become an inescapable issue. Previous research has found the cross-sectional association between loneliness and depression, but their codevelopment has been understudied. Therefore, exploring the codevelopment and its correlates has significant implications for prevention and healthcare professionals. DESIGN: A longitudinal follow-up study. METHODS: The study used nationally representative data over a 14-year follow-up period from the Taiwan Longitudinal Study on Ageing focused on Taiwanese aged 60 years and above (n = 4049). Group-based trajectory modelling, group-based dual-trajectory modelling and multinomial logistic regression were the primary analytical methods. RESULTS: We identified three distinct dual trajectories of loneliness and depression: longitudinal low-frequency lonely depressed (29.3%), longitudinal moderate-frequency lonely depressed (59.4%) and longitudinal high-frequency lonely depressed (11.3%). After considering several demographic and background characteristics, difficulty in physical functioning, number of physical symptoms and diseases, sleep quality and number of child deaths were found to be significantly associated. CONCLUSION: Across the three identified dual-trajectory groups, they all showed a stable loneliness frequency pattern over time; however, the moderate-frequency group and high-frequency group both had a trajectory of increasing depression. It seems that depression tends to change over time in a worsening direction, especially for those with a certain frequency of loneliness. Furthermore, differences in individual and family correlates were found across the groups. IMPLICATIONS FOR PRACTICE: Interventions focusing on the specific factors may help hinder coexisting loneliness and depression, and have implications for developing health promotion strategies and chronic disease care plans.

Impact of statin on long-term outcome among patients with end-stage renal disease with acute myocardial infarction (AMI): a nationwide case-control study.

BACKGROUND: Use of statin has been associated with reduced risk of cardiovascular diseases events and mortality. However, in patients with end-stage renal disease (ESRD), the protective effects of statin are controversial. To evaluate the impact of chronic statin use on clinical outcomes of patients with acute myocardial infarction (AMI) with ESRD. METHODS: We enrolled 8056 patients with ESRD who were initially diagnosed and admitted for first AMI from Taiwan's National Health Insurance Research Database. Of which, 2134 patients underwent statin therapy. We randomly selected and use age, sex, hypertension, diabetes mellitus (DM), peripheral vascular diseases (PVD), heart failure (HF), cerebrovascular accidents (CVA), chronic obstructive pulmonary disease, matched with the study group as controls (non-stain user). We compared the effects of statin use in term of all-cause death among patients with AMI with ESRD. RESULTS: Statin use resulted in a significantly higher survival rate in patients ith AMI with ESRD compared with non-statin users. After adjusted the comorbidities the male patients and patients with DM, PVD, HF and CVA had lower long-term survival rate (all p<0.001). Patients who underwent percutaneous coronary intervention (p<0.001), ACE inhibitors/angiotensin II receptor blockers (p<0.001), ß receptor blockers (p<0.001) and statin therapy (p=0.007) had better long-term survival rate. Patients with AMI with ESRD on statin therapy exhibited a significantly lower risk of mortality compared with non-statin users (p<0.0001). CONCLUSION: Among patients with ESRD with AMI, statin therapy was associated with reduced all-cause mortality.

Effects of epinephrine on heart rate variability and cytokines in a rat sepsis model.

Catecholamines have both anti-inflammatory and vasoactive properties. A decreased cardiac response to catecholamines has been associated with a high risk of death in sepsis and septic shock. The aim of this study was to investigate the effects of epinephrine (EPI) on heart rate variability (HRV) and autonomic balance, as well as cytokine levels, in a rat sepsis model. Thirty-six male Sprague-Dawley rats were assigned to 4 experimental groups and 2 control groups of 6 rats each. The rats in the experimental groups were inoculated with a lipopolysaccharide (LPS, endotoxin) to establish a sepsis model. Group A received only LPS; group B received LPS, antecedent EPI and the nonselective ß-blocker propranolol; group C received LPS and antecedent EPI; and group D received LPS, antecedent EPI and the selective ß1-blocker esmolol. One control group received EPI and the other received saline placebo. Heart rate variability (HRV) was analyzed and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) levels were measured. Measurements were carried out at baseline, at 0 hour after EPI infusion, and at 0.5, 2, and 4 hours after LPS inoculation. There were significant differences in HRV and cytokine levels between the groups, indicating that LPS infusion caused autonomic imbalance. Antecedent EPI significantly decreased the level of TNF-α in group C compared with group A in which TNF-α level peaked at 2 hours and then declined. Propranolol (group B) but not esmolol (group D) administration resulted in elevated TNF-α levels, comparable to those observed in group A. In conclusion, antecedent administration of EPI in a rat sepsis model inhibits the production of TNF-α possibly via the ß2-adrenoceptor.

Dexamethasone Downregulates Expressions of 14-3-3ß and γ-Isoforms in Mice with Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection.

Steroids are commonly used in patients with eosinophilic meningitis caused by A. cantonensis infections. The mechanism steroids act on eosinophilic meningitis remains unclear. In this mouse experiments, expressions of 14-3-3 isoform ß and γ proteins significantly increased in the CSF 2-3 weeks after the infection, but not increasedin the dexamethasone-treated group. Expression of 14-3-3 ß, γ, ε, and θ isoforms increased in brain meninges over the 3-week period after infection and decreased due to dexamethasone treatment. In conclusion, administration of dexamethasone in mice with eosinophilic meningitis decreased expressions of 14-3-3 isoform proteins in the CSF and in brain meninges.

Caffeic Acid Phenethyl Ester Rescues Pulmonary Arterial Hypertension through the Inhibition of AKT/ERK-Dependent PDGF/HIF-1α In Vitro and In Vivo.

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial proliferation and remodeling, resulting in a specific increase in right ventricle systolic pressure (RVSP) and, ultimately right ventricular failure. Recent studies have demonstrated that caffeic acid phenethyl ester (CAPE) exerts a protective role in NF-κB-mediated inflammatory diseases. However, the effect of CAPE on PAH remains to be elucidated. In this study, monocrotaline (MCT) was used to establish PAH in rats. Two weeks after the induction of PAH by MCT, CAPE was administrated by intraperitoneal injection once a day for two weeks. Pulmonary hemodynamic measurements and pulmonary artery morphological assessments were examined. Our results showed that administration of CAPE significantly suppressed MCT-induced vascular remodeling by decreasing the HIF-1α expression and PDGF-BB production, and improved in vivo RV systolic performance in rats. Furthermore, CAPE inhibits hypoxia- and PDGF-BB-induced HIF-1α expression by decreasing the activation of the AKT/ERK pathway, which results in the inhibition of human pulmonary artery smooth muscle cells (hPASMCs) proliferation and prevention of cells resistant to apoptosis. Overall, our data suggest that HIF-1α is regarded as an alternative target for CAPE in addition to NF-κB, and may represent a promising therapeutic agent for the treatment of PAH diseases.

Idiopathic Pulmonary Arterial Hypertension Was Diagnosed Initially by the Computed Tomographic Angiogram.

Idiopathic pulmonary arterial hypertension (IPAH) is a rare and progressive disease with non-specific signs and symptoms. A 50-year-old woman with IPAH presented to the emergency department (ED) with a complaint of episodic dyspnea that had persisted for the previous two months. Based on the fi ndings of the initial chest computed tomographic angiography conducted in the ED, we suspected pulmonary hypertension. IPAH was eventually confi rmed following a series of investigations, including right heart catheterization. The history of this interesting case is reported with a review of the relevant literature.

Application of time series analysis in modelling and forecasting emergency department visits in a medical centre in Southern Taiwan.

OBJECTIVE: Emergency department (ED) overcrowding is acknowledged as an increasingly important issue worldwide. Hospital managers are increasingly paying attention to ED crowding in order to provide higher quality medical services to patients. One of the crucial elements for a good management strategy is demand forecasting. Our study sought to construct an adequate model and to forecast monthly ED visits. METHODS: We retrospectively gathered monthly ED visits from January 2009 to December 2016 to carry out a time series autoregressive integrated moving average (ARIMA) analysis. Initial development of the model was based on past ED visits from 2009 to 2016. A best-fit model was further employed to forecast the monthly data of ED visits for the next year (2016). Finally, we evaluated the predicted accuracy of the identified model with the mean absolute percentage error (MAPE). The software packages SAS/ETS V.9.4 and Office Excel 2016 were used for all statistical analyses. RESULTS: A series of statistical tests showed that six models, including ARIMA (0, 0, 1), ARIMA (1, 0, 0), ARIMA (1, 0, 1), ARIMA (2, 0, 1), ARIMA (3, 0, 1) and ARIMA (5, 0, 1), were candidate models. The model that gave the minimum Akaike information criterion and Schwartz Bayesian criterion and followed the assumptions of residual independence was selected as the adequate model. Finally, a suitable ARIMA (0, 0, 1) structure, yielding a MAPE of 8.91%, was identified and obtained as Visitt=7111.161+(at+0.37462 at-1). CONCLUSION: The ARIMA (0, 0, 1) model can be considered adequate for predicting future ED visits, and its forecast results can be used to aid decision-making processes.

Disseminated Nocardiosis with Lung, Liver and Spleen Abscesses in Sweet Syndrome: A Case Report.

Hepatic abscesses are rarely encountered in disseminated nocardia infections. We report a rare case of idiopathic Sweet syndrome (SS) who responded well to steroid therapy. However, he developed multiple abscesses in the lung, liver and spleen after 6 months of systemic steroid therapy. The culture result from liver abscess and sputum was diagnostic of disseminiated nocardiosis. Intravenous sulfamethoxazole/trimethoprim was given and follow-up computed tomography (CT) scan revealed resolution of abscess. To conclude, nocardiosis should be suspected as a likely cause of lung, liver and spleen abscesses in patients undergoing long-term steroid treatment. A high index of clinical suspicion in patients with defects in cell-mediated immunity and prompt management by appropriate image studies are needed to prevent delay in diagnosis.

High daily doses of trimethoprim/sulfamethoxazole are an independent risk factor for adverse reactions in patients with pneumocystis pneumonia and AIDS.

BACKGROUND: Trimethoprim/sulfamethoxazole (TMP/SMX) is currently the most effective therapeutic agent for Pneumocystis jirovecii pneumonia (PJP) in patients with AIDS. The major drawback is the frequent occurrence of adverse reactions (ADRs).The current study was designed to determine the frequency and risk factors for TMP/SMX-related ADRs among patients with PJP and AIDS. METHODS: A retrospective study was conducted in adult patients with PJP and AIDS who were admitted to the Veterans General Hospital in, Kaohsiung, Taiwan between January 2006 and December 2011. Charts were reviewed to determine the effect of age, risk behaviors, severity of illness, viral load, CD4 cell counts, use of corticosteroids, and dosage and duration of TMP/SMX on ADRs during hospitalization. Patients who received TMP/SMX for ≤ 5 days or with an incomplete medical record were excluded. Multivariate logistic regression was used to calculate the hazard ratio (HR) for ADRs. RESULTS: Fifty two of 75 patients with PJP and AIDS met the study criteria. Of these patients, 21/52 (40.3%) developed an ADR. Among the 21 patients who suffered an ADR, skin rash was noted in 10 (47.6%), liver function impairment in nine (42.9%), elevated creatinine in eight (38.1%), fever in four (19%), and gastrointestinal symptoms in three (14.3%). Most of the ADRs occurred within the 1(st) 2 weeks of TMP/SMX therapy. Cox proportional hazards analysis revealed that a daily dose of TMP/SMX of ≥ 16 mg/kg (HR, 3.8; 95% confidence interval, 1.40-10.35; p = 0.009) and age 34 years (HR, 4.30; 95% confidence interval, 1.52-12.14; p = 0.006) were independently associated with ADRs. CONCLUSION: We found a high incidence of ADRs among patients with PJP and AIDS treated with TMP/SMX, and most involved the skin and liver. A daily dose of ≥ 16 mg/kg of TMP/SMX and age 34 years were independent risk factors for ADRs.

Contribution of Hepatitis B to Long-Term Outcome Among Patients With Acute Myocardial Infarction: A Nationwide Study.

Although a possible association between hepatitis B and cardiovascular disease has been identified, the impact of viral hepatitis B on long-term prognosis after an acute myocardial infarction (AMI) is uncertain. Therefore, the aim of our study was to evaluate the specific impact of viral hepatitis B on survival after a first AMI through a retrospective analysis of data from the Taiwan National Health Insurance Research Database.This was a nationwide, propensity score-matched case-control study of patients admitted to hospitals between January 2000 and December 2012 with a primary diagnosis of a first AMI. Among the 7671 prospective patients, 244 patients with a confirmed diagnosis of viral hepatitis B infection were identified. A propensity score, one-to-one matching technique was used to match 244 controls to the AMI group for analysis. Controls were matched on the following variables: sex, age, hypertension, dyslipidemia, diabetes, peripheral vascular disease, heart failure, cerebrovascular accidents, end-stage renal disease, chronic obstructive pulmonary disease, and percutaneous coronary intervention (PCI).Overall, viral hepatitis B infection did not influence the 12-year survival rate (P = 0.98). However, survival was lower in female patients with viral hepatitis B infection compared to those without (P = 0.03; hazard ratio, 1.79; 95% confidence interval, 1.08-2.94). Inclusion of percutaneous coronary management improved survival, independent of sex, age, or hepatitis B status.Hepatitis B infection might increase the mortality risk of female patients after a first AMI. PCI may improve the long-term survival of patients after a first AMI, regardless of sex, age, and hepatitis B status.

Therapeutic Benefits of Induced Pluripotent Stem Cells in Monocrotaline-Induced Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is characterized by progressive increases in vascular resistance and the remodeling of pulmonary arteries. The accumulation of inflammatory cells in the lung and elevated levels of inflammatory cytokines in the bloodstream suggest that inflammation may play a role in PAH. In this study, the benefits of induced pluripotent stem cells (iPSCs) and iPSC-conditioned medium (iPSC CM) were explored in monocrotaline (MCT)-induced PAH rats. We demonstrated that both iPSCs and iPSC CM significantly reduced the right ventricular systolic pressure and ameliorated the hypertrophy of the right ventricle in MCT-induced PAH rats in models of both disease prevention and disease reversal. In the prevention of MCT-induced PAH, iPSC-based therapy led to the decreased accumulation of inflammatory cells and down-regulated the expression of the IL-1ß, IL-6, IL-12α, IL-12ß, IL-23 and IFNγ genes in lung specimens, which implied that iPSC-based therapy may be involved in the regulation of inflammation. NF-κB signaling is essential to the inflammatory cascade, which is activated via the phosphorylation of the NF-κB molecule. Using the chemical inhibitor specifically blocked the phosphorylation of NF-κB, and in vitro assays of cultured human M1 macrophages implied that the anti-inflammation effect of iPSC-based therapy may contribute to the disturbance of NF-κB activation. Here, we showed that iPSC-based therapy could restore the hemodynamic function of right ventricle with benefits for preventing the ongoing inflammation in the lungs of MCT-induced PAH rats by regulating NF-κB phosphorylation.

A rare but potentially lethal case of tuberculous aortic aneurysm presenting with repeated attacks of abdominal pain.

Tuberculous aortic aneurysm is an extremely rare disease with a high mortality rate. The clinical features of this condition are highly variable, ranging from asymptomatic with or without constitutional symptoms, abdominal pain to frank rupture, bleeding and shock. We herein report the case of a 56-year-old man with a large tuberculous mycotic aneurysm in the abdominal aorta with an initial presentation of repeated attacks of abdominal pain lasting for several months. Due to the vague nature of the initial symptoms, tuberculous aortic aneurysms may take several months to diagnose. This case highlights the importance of having a high index of suspicion and providing timely surgery for this rare but potentially lethal disease.

Chemokine co-receptor usage in HIV-1-infected treatment-naïve voluntary counselling and testing clients in Southern Taiwan.

OBJECTIVE: The goal of this present study was to determine the proportion of CCR5-tropic and CXCR4-tropic viruses and impact of tropism test on clinical presentation, CD4 cell counts, viral load and genotypic drug resistance from drug-naïve, voluntary counselling and testing (VCT) clients in southern Taiwan. DESIGN: This was a cross-sectional study. Plasma samples were collected from HIV-1-infected patients from January 2013 to December 2013; subjects were recruited from free VCT centres in southern Taiwan. SETTING: Taiwan. PARTICIPANTS: Plasma samples from 108 HIV-1-infected, treatment-naïve, VCT clients were analysed. HIV-1 strains were sequenced, genotype resistance was determined by a commercial kit (Viro-seq) and co-receptor tropism (CRT) was predicted by an internet tool geno2pheno[coreceptor], with a 10% false-positive rate as the cut-off. Differences in progression markers, patient characteristics, VCT questionnaires and HIV subtype distribution were evaluated statistically. RESULTS: All the 108 VCT clients were male with 90% between the ages of 20 and 40 years. Eighty-eight per cent of the patients were men who have sex with men (MSM). The median (IQR) CD4 cell count was 342 cells/µL (221-454) and the viral load was 4.6 log (4.0-5.0). HIV-transmitted drug resistance was found in 9.3% (10/108) of the patients. CRT predictions indicated that 74% of the patients had only R5-tropic strains. CRT was not associated with CD4 cell counts, patient characteristics, VCT questionnaire and transmitted drug resistance. There was a significant difference with regard to viral load at the time of presentation, showing that patients with R5 more often had a higher viral load as compared with those with X4/DM strains (4.6±0.6 log vs 4.33±0.7 log, p=0.036). CONCLUSIONS: We found that 74% of the VCT clients were infected with R5-tropic virus strains. HIV-transmitted drug resistance was not associated with CRT predictions. Higher viral load at presentation was predictive of R5 co-receptor usage.

Recurrent Hypokalemic Periodic Paralysis Unmasks Sjogren Syndrome without Sicca Symptoms.

Hypokalemic Periodic Paralysis (HPP) may occur as a rare complication of Sjogren Syndrome (SS) and Renal Tubular Acidosis (RTA). A 64-year male patient came with HPP, and was later diagnosed with distal RTA. The patient, who had no xerostomia and xerophthalmia, was diagnosed with primary SS from serologic and histologic findings of minor salivary gland biopsy. The patient recovered after potassium replacement therapy. Renal biopsy was also performed and revealed evidence of tubulointerstitial nephritis. Corticosteroids were administered and there was no recurrence of HPP during a 4-year follow-up period. The case highlights the significance of acute hypokalemia management in emergency department as it can unmask SS even if the SS is not associated with sicca symptoms. Hypokalemic paralysis associated with normal anion gap metabolic acidosis should prompt toward the diagnosis of SS.

Hepatic angiosarcoma may have fair survival nowadays.

Hepatic angiosarcoma (HAS) is rare but often fatal. A review of literature in 1979 found that only 3% of the 70 patients lived for more than 2 years, but the survival might have been improved over the years. We conducted a retrospective study and reviewed the medical records of patients who visited a teaching hospital in Taiwan from January 2000 to August 2010 and had pathological proof of HAS. In addition, we conducted a review of literature and compared those who survived for 2 years or more to those who did not. Of the 3503 patients with primary liver cancer we identified, 9 had HAS, of whom 3 (33.3%) survived for 2 years or more. One survived for 24 months without surgical resection, and the other two received surgery with postoperative chemotherapy and were still alive 32 and 37 months later, respectively. Through reviewing literature, we identified 3 more patients in Taiwan who had survived for 2 years or more. One survived for 42 months without surgical resection, the other two received segmentectomy with postoperative chemotherapy or radiotherapy. We also identified 8 such cases outside Taiwan, including 1 who received chemotherapy without surgery and survived for 53 months. None of the differences in the clinical characteristics between those who had and had not survived for 2 years or more reached statistical significance. In conclusion, we believe the combination of surgery and adjuvant chemotherapy may be able to achieve long-term survival in some HAS patients nowadays, and it is even possible to achieve fair survival using chemotherapy alone.

Dexamethasone inhibits brain apoptosis in mice with eosinophilic meningitis caused by Angiostrongylus cantonensis infection.

BACKGROUND: Angiostrongylus cantonensis, the rat lungworm, is the major cause of eosinophilic meningitis worldwide. Rats serve as the definitive host of the nematode, but humans can be infected incidentally, leading to eosinophilic meningitis. A previous BALB/c animal study has demonstrated increased apoptotic proteins and decreased anti-apoptotic proteins in mice infected with A. cantonensis. Steroids may be an effective treatment option for eosinophilic meningitis caused by A. cantonensis, but the involved mechanism is unclear. This study hypothesized that the beneficial effects of steroids on eosinophilic meningitis are mediated by decreased apoptosis. METHODS: In a BALB/c animal model, mice were orally infected with 50 A. cantonensis L3 via an oro-gastric tube and were sacrificed every week for 3 consecutive weeks after infection or until the end of the study. Dexamethasone was injected intra-peritoneally from the 7(th) day post-infection until the end of the 21-day study. Evans blue method was used to measure changes in the blood brain barrier, while western blotting, immuno-histochemistry, and TUNEL assay were used to analyze brain homogenates expression of apoptotic and anti-apoptotic proteins. RESULTS: There were increased amounts of Evans blue, apoptotic proteins (caspase-3, -8, and -9 and cytochrome C), and decreased anti-apoptotic proteins (bcl-2) after 2-3 weeks of infection. Dexamethasone administration significantly decreased Evans blue extravasations and apoptotic protein expressions. CONCLUSIONS: Apoptosis of mice brain homogenates can be repressed by dexamethasone treatment.

Ankylosing spondylitis associated with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a frequent complication of connective tissue diseases, such as systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis. However, the occurrence of PAH in a patient with ankylosing spondylitis (AS) has not been previously reported with a detailed clinical description in the English literature. We herein report the first case of AS associated PAH in a 27-year-old Taiwanese man with a chief complaint of intermittent palpitations lasting for two years. To the best of our knowledge, this is the first reported case of AS associated with PAH with a detailed clinical description and findings of right heart catheterization published in the English literature.