Screening for esophagitis and Barrett's esophagus with wireless esophageal capsule endoscopy: a multicenter prospective trial in patients with reflux symptoms

BACKGROUND AND AIM: Esophageal capsule endoscopy (ECE) is a new technology that allows noninvasive investigation of the esophagus. Our aim was to evaluate prospectively the diagnostic yield of ECE in patients with chronic reflux symptoms. PATIENTS AND METHODS: Eighty-nine patients (40 men, mean age 54 yr) referred to five endoscopic centers for esophagogastroduodenoscopy (EGD) were enrolled. Patients first underwent ECE, then EGD; endoscopists who performed the EGD were blind to the ECE data that were interpreted separately by two independent readers. The Los Angeles, Prague, and Montreal classification systems were used to describe endoscopic findings. RESULTS: Seventy-seven patients completed the study. Esophagitis and endoscopically suspected esophageal metaplasia (ESEM) were present in 24 and 10 patients, respectively. Columnar lining was histologically confirmed in seven patients (3 with specialized intestinal metaplasia and 4 with gastric metaplasia). The kappa values for interobserver agreement regarding the diagnosis of esophagitis and ESEM were 0.67 (0.49-0.85) and 0.49 (0.17-0.81), respectively. The diagnostic yields of ECE to detect esophagitis and ESEM were as follows: sensitivity 79% and 60%, specificity 94% and 100%, positive predictive value (PPV) 83% and 100%, negative predictive value (NPV) 92% and 95%, respectively. CONCLUSION: As a screening tool in patients with reflux symptoms, ECE has an excellent specificity and NPV for the diagnosis of esophagitis and ESEM. However, its sensitivity for the diagnosis of ESEM is not optimal. Further studies are necessary to improve the procedure, and to compare the cost-effectiveness of strategies using ECE or EGD.     

Doxazosin in the treatment of patients with mild or moderate hypertension and mild or moderate renal insufficiency

The antihypertensive efficacy and safety of doxazosin, a selective α₁-inhibitor, were assessed in 23 hypertensive patients with renal insufficiency. The study involved three phases: (1) a 2-week baseline period, (2) a 10-week period during which patients received doxazosin, 1 to 16 mg, once daily, and (3) a 4-week maintenance period. After 14 weeks of active treatment, systolic/diastolic blood pressures of efficacy evaluable patients were reduced by $\text{8.9}\text{9.2}$ and $\text{4.6}\text{9.1}\text{mm Hg}$ to final values of $\text{153}\text{90}$ and $\text{149}\text{91}\text{mm Hg}$ in the supine and standing positions, respectively. The mean dose of the efficacy evaluable patients was 9.8 mg/day. Eleven patients experienced one or more side effects, most of which were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. There were no significant differences in serum creatinine levels between baseline and final visits. The overall lipid profile indicated a decrease in total cholesterol with increases in high-density lipoprotein cholesterol and the high-density lipoprotein/total cholesterol ratio. From baseline to final visit there was highly significant reduction of 19% (p < 0.05) in calculated risk scores for coronary heart disease on the basis of the Framingham equation.     

Procalcitonin algorithm to guide initial antibiotic therapy in acute exacerbations of COPD admitted to the ICU: a randomized multicenter study

Purpose

To compare the efficacy of an antibiotic protocol guided by serum procalcitonin (PCT) with that of standard antibiotic therapy in severe acute exacerbations of COPD (AECOPDs) admitted to the intensive care unit (ICU).

Methods

We conducted a multicenter, randomized trial in France. Patients experiencing severe AECOPDs were assigned to groups whose antibiotic therapy was guided by (1) a 5-day PCT algorithm with predefined cutoff values for the initiation or stoppage of antibiotics (PCT group) or (2) standard guidelines (control group). The primary endpoint was 3-month mortality. The predefined noninferiority margin was 12%.

Results

A total of 302 patients were randomized into the PCT (n?=?151) and control (n?=?151) groups. Thirty patients (20%) in the PCT group and 21 patients (14%) in the control group died within 3 months of admission (adjusted difference, 6.6%; 90% CI ??0.3 to 13.5%). Among patients without antibiotic therapy at baseline (n?=?119), the use of PCT significantly increased 3-month mortality [19/61 (31%) vs. 7/58 (12%), p?=?0.015]. The in-ICU and in-hospital antibiotic exposure durations, were similar between the PCT and control group (5.2?±?6.5 days in the PCT group vs. 5.4?±?4.4 days in the control group, p?=?0.85 and 7.9?±?8 days in the PCT group vs. 7.7?±?5.7 days in the control group, p?=?0.75, respectively).

Conclusion

The PCT group failed to demonstrate non-inferiority with respect to 3-month mortality and failed to reduce in-ICU and in-hospital antibiotic exposure in AECOPDs admitted to the ICU.

     

Phylogenetic character mapping of proteomic diversity shows high correlation with subspecific phylogenetic diversity in Trypanosoma cruzi

We performed a phylogenetic character mapping on 26 stocks of Trypanosoma cruzi, the parasite responsible for Chagas disease, and 2 stocks of the sister taxon T. cruzi marinkellei to test for possible associations between T. cruzi-subspecific phylogenetic diversity and levels of protein expression, as examined by proteomic analysis and mass spectrometry. We observed a high level of correlation (P < 10(-4)) between genetic distance, as established by multilocus enzyme electrophoresis, and proteomic dissimilarities estimated by proteomic Euclidian distances. Several proteins were found to be specifically associated to T. cruzi phylogenetic subdivisions (discrete typing units). This study explores the previously uncharacterized links between infraspecific phylogenetic diversity and gene expression in a human pathogen. It opens the way to searching for new vaccine and drug targets and for identification of specific biomarkers at the subspecific level of pathogens.     

Inferior vena cava agenesis and deep vein thrombosis: 10 patients and review of the literature

Inferior vena cava agenesis (IVCA) is a rare condition, found in almost 5% of patients under 30 years old with unprovoked deep venous thrombosis (DVT). We describe 10 consecutive patients with IVCA-associated DVT and conducted an extensive literature review to investigate the typical spectrum of IVCA-associated DVT. Among our patients (eight men and two women; mean age, 25 ± 4.5 years), DVT followed intense and unusual (major) physical activity for eight of them. DVT was bilateral in six patients and unilateral in four. Ultrasonography was unable to detect IVCA, which was visualized by computed-tomography scans for seven patients, and magnetic resonance imaging and angiography for 10. Hereditary thrombophilia screening, to detect factor V Leiden or prothrombin gene heterozygosity (G20210A mutation), was positive for only two patients. Wearing elastic stockings and taking an indefinite or long-term vitamin K antagonist were prescribed for all 10 patients and nine complied with the latter. To date, 62 patients with IVCA-associated DVT have been reported in the English literature. Analysis of them and our patients yielded a typical spectrum of IVCA-associated DVT characteristics: IVCA occurs in young adults, particularly males, and is revealed by proximal DVT following major physical exertion. All were treated with a prolonged vitamin K antagonist and advised to wear elastic stockings. No precise duration of anticoagulation has been established.     

BRCA1, BRCA2, AR and IGF-I expression in prostate cancer: correlation between RT-qPCR and immunohistochemical detection

Identification and characterization of biomarkers in prostate cancer are important for improving the diagnosis. The aim of this study was to determine differences in the expression of 4 genes according to the stage of malignancy in prostate cancer. We analyzed BRCA1, BRCA2, androgen receptor (AR) and IGF-I gene expression in a cohort of 98 prostate biopsies. We used TaqMan RT-qPCR for mRNA detection, and correlation with proteins was performed using immunohistochemistry. Among the 98 studied prostate biopsies, high heterogeneity in the expression of the 4 genes was detected among the different histological types. However, down-regulation of BRCA1 and BRCA2 mRNA was detected, particularly in the normal tissues. The expression of AR was dependent on the stage of the tumor. The IGF-I gene was specifically expressed in the tumor tissues. Upon comparison between protein and mRNA expression for BRCA1, BRCA2 and AR, we obtained a trend; however, this did not achieve statistical significance. Regarding IGF-I, a correlation between mRNA expression and staining intensity of the protein was found to be significant (p<0.012). The AR biomarker was found to be slightly correlated with the prostate cancer diagnosis (p=0.013). AR was found to be decreased in the tumors with a 43% sensitivity and 90% specificity. The relative risk of 2.05 (1.13-3.69) indicated a 2?fold higher chance of cancer occurrence when AR was ≤0.206.