Prognostic factors in diffuse malignant pleural mesothelioma: effects of pretreatment clinical and laboratory characteristics

AbstractThe aim of this study was to investigate the effects of various pretreatment clinical and laboratory characteristics on the survival of patients with diffuse malignant pleural mesothelioma (DMPM). One hundred histopathologically confirmed DMPM patients were evaluated. Fifty-nine were treated with chemoimmunotherapy, while 41 who had refused chemoimmunotherapy received supportive therapy alone. The following pretreatment characteristics were evaluated in both univariate and multivariate Cox regression analyses: age, gender, Karnofsky performance score (KPS), histology, asbestos exposure, presence of chest pain, dyspnoea, weight loss, symptom duration, smoking history, disease location, platelet count, haemoglobin, white blood cell (WBC) count, serum lactate dehydrogenase (LDH) and extent of disease (stage). Univariate analysis showed that patients with age ≥75 years, male gender, smoking history, advanced stages above stage I disease, KPS <70, WBC count ≥8450 and LDH level ≥500 IU l−1have a worse prognosis. With multivariate Cox regression analyses, age ≥75 years, advanced stages above stage I disease, KPS <70 and LDH level ≥500 IU l−1were found to be indicators of a poorer prognosis. In conclusion, in our study each of low performance status, older age, advanced stage disease, high LDH level and prognosis were found to be related

Interaction of atopy and smoking on respiratory effects of occupational dust exposure: a general population-based study

BACKGROUND: For individual exposures, effect modification by atopy or smoking has been reported on the occurrence of occupational airway disease. It is unclear if effect modification can be studied in a general population by an aggregated exposure measure. Assess relationship between airway obstruction and occupational exposure using a job-exposure-matrix (JEM) classifying jobs into 3 broad types of exposure, and test for effect modification by atopy, and smoking. METHODS: Data from 1,906 subjects were analyzed, all participants of the European Community Respiratory Health Survey. Job titles were categorized by an a priori constructed job exposure matrix into three classes of exposure to respectively organic dust, mineral dust, and gases/ fumes. Relationships were assessed for 'current wheeze', bronchial hyperresponsiveness (BHR), 'current asthma' (wheeze+BHR), and 'chronic bronchitis' (morning phlegm or morning cough), and lung function. RESULTS: Subjects with organic dust exposure in their work environment more frequently had 'current asthma' (OR 1.48, 95% C.I. 0.95;2.30), and a lower FEV(1 )(-59 mL, 95% C.I. -114;-4). The relationship was only present in asthmatic workers, and their risk was four-fold greater than in subjects with either atopy or exposure alone. Mineral dust exposure was associated with 'chronic bronchitis' (OR 2.22, 95% C.I. 1.16;4.23) and a lower FEV(1)/FVC ratio (-1.1%, 95% C.I. -1.8;-0.3). We observed an excess risk in smokers, greater than the separate effects of smoking or mineral dust exposure together. CONCLUSION: Occupational exposure to organic dust is associated with an increased risk of asthma, particularly in atopics. Chronic bronchitis occurs more frequently among individuals exposed to mineral dust, and smoking doubles this risk

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo

Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO2 challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a β-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any β-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.—Palpant, N. J., D'Alecy, L. G., Metzger, J. M. Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo