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The article presents the result of a study which analyzed c-Myc oncoprotein levels and disability of the dihydrofolate reductase (DHFR) gene in cervical tissue biopsies. The researchers used fluorescence in situ hybridization (FISH) to examine the stability of the DHFR gene, while they used quantitative fluorescent immunohistochemistry to evaluate c-Myc protein levels. They reported the integration of human papillomavirus (HPV) next to the N-myc gene and c-Myc gene.

Background: There are only limited data about peri-interventional pain during cardiac electrophysiological procedures without analgosedation. In this study, peri-interventional pain and recollection of it after the intervention were evaluated., Methods: A total of 101 patients (43 electrophysiological/ablation procedures and 58 device surgeries) reported pain on a numerical rating scale (NRS; 0-10) before (pre), during (peri), and after (post) the intervention. Maximum pain (maxNRS) and the average of pain (meanNRS) were used for statistical analysis. Peri-interventional pain was compared with postinterventional data of the recollection of peri-interventional pain (peri-post). Patients were allocated into 2 groups (with 51 and 50 patients, respectively) to evaluate the mode of patient-staff interaction on pain recollection. Depressive, anxiety, and somatic symptom scales (Patient Health Questionnaire-15, Generalized Anxiety Disorder-7, and Patient Health Questionnaire-15) were used to analyze their influence on pain recollection., Results: In total, 49.6% of patients (n = 50) complained of moderate to severe pain (maxNRS) at least once during the procedure. The comparison between peri and peri-post data revealed the following (median (range)-maxNRS, peri: 3 (0-10) versus peri-post: 4 (0-9) (ns), and meanNRS, peri: 1.4 (0-7) versus peri-post: 2.0 (0-6) (ns). The mode of patient-staff interaction had no influence on pain. No effect was found for psychosocial factor concerning pain and the recollection of pain. The results of the linear regression showed no influence of low-dose midazolam on recollection of pain., Conclusion: Half of the patients reported moderate to severe pain at least once during cardiac electrophysiological procedures without analgosedation. However, on average, patients reported only low pain levels. Postinterventional derived data on discomfort reflect the peri-interventional situation.

Background: Current guidelines recommend non-vitamin K antagonist oral anticoagulants (NOACs) as the first-choice therapy in patients with nonvalvular atrial fibrillation because these drugs have several benefits over the vitamin K antagonists (VKAs). It is unknown whether these benefits remain when NOACs have to be combined with aspirin therapy. To assess the efficacy and safety of NOACs compared with VKAs in patients with atrial fibrillation and concomitant aspirin therapy, we conducted a systematic review and study-based meta-analysis of published randomized controlled trials., Methods: A systematic electronic literature search was done in MEDLINE, EMBASE, and Cochrane CENTRAL Register of Controlled Trials for studies including published data of patients ≥18 years of age with nonvalvular atrial fibrillation, randomized to either VKAs or NOACs, or receiving aspirin therapy at any time during the study that report all-cause stroke or systemic embolism, vascular death, myocardial infarction, major bleeding, or intracranial hemorrhage as an outcome. Hazard ratios (HRs) with 95% confidence intervals (CIs) for each outcome were extracted from the individual studies and pooled with random-effects meta-analysis., Results: This study-based meta-analysis was restricted to the subgroups of patients on aspirin therapy (n=21 722) from 4 randomized controlled trials comparing VKAs and NOACs (n=71 681) in nonvalvular atrial fibrillation. In this meta-analysis including patients on mainly low-dose aspirin, NOACs were found to be more effective (outcome of stroke or systemic embolism: HR, 0.78; 95% CI, 0.67-0.91; vascular death: HR, 0.85; 95% CI, 0.76-0.93) and as safe as VKAs with respect to major bleeding (HR, 0.83; 95% CI, 0.69-1.01). NOACs were safer with respect to the reduction of intracranial hemorrhage (HR, 0.38; 95% CI, 0.26-0.56)., Conclusions: This study-based meta-analysis shows that it may be both safer and more effective to use NOACs compared with VKAs to treat patients with nonvalvular atrial fibrillation and concomitant aspirin therapy., (© 2017 American Heart Association, Inc.)

Background: Inducibility of ventricular tachycardia (VT) has limited ability to predict recurrent VT after catheter ablation (CA). We sought to correlate the signal-averaged ECG (SAECG) with the endocardial scar characteristics in patients with ischemic VTs. We suggest that successful CA can result in normalization of the SAECG., Methods and Results: Fifty patients (42 male; aged 67±10 years, ejection fraction 34±12%) with ischemic VTs were prospectively enrolled. SAECG was performed before and after CA. Patients with at least 2 abnormal criteria (filtered QRS ≥114 ms; root mean square 40 <20 μV, and low-amplitude potentials 40 >38 ms) were defined as having positive SAECG. There was a linear correlation between endocardial scar area (<1.5 mV) and filtered QRS (r=0.414; P=0.003). CA resulted in normalization of the SAECG in 6 patients. In patients with filtered QRS ≤120 ms, 13 (40.6%) patients had normal SAECG after CA compared with 7 (21.9%) before ablation (P=0.034). Patients with normal or normalized SAECG after CA had better VT-free survival compared with those whose SAECG remained abnormal. Abnormal SAECG after CA was a predictor for VT recurrence: hazard ratio=3.64; P=0.039 for the overall population, and hazard ratio=5.80; P=0.022 for patients having QRS ≤120 ms., Conclusions: There is a significant correlation between the surface SAECG and endocardial scar size in patients with ischemic VTs. A successful CA can result in normalization of SAECG that is associated with more favorable long-term outcomes. SAECG can be useful to assess the procedural success of VT ablation., (© 2016 American Heart Association, Inc.)

The aim of this study was to determine the antibiotic susceptibility profiles of bacteria in bile samples and to analyze the clinical relevance of the findings as only limited information about risk factors for elevated frequence of bacterial and fungal strains in routinely collected bile samples has been described so far.A prospective cohort study at a tertiary care center was conducted. Seven hundred forty-four patients underwent 1401 endoscopic retrograde cholangiographies (ERCs) as indicated by liver transplantation (427/1401), primary sclerosing cholangitis (222/1401), choledocholithiasis only (153/1401), obstruction due to malignancy (366/1401), or other conditions (233/1401). Bile samples for microbiological analysis were obtained in all patients.The 71.6% (823/1150) samples had a positive microbiological finding, and 57% (840/1491) of the bacterial isolates were gram-positive. The main species were Enterococcus spp (33%; 494/1491) and Escherichia coli (12%; 179/1491). Of the samples, 53.8% had enteric bacteria and 24.7% had Candida spp; both were associated with clinical and laboratory signs of cholangitis (C-reactive proteins 35.0 ± 50.1 vs 44.8 ± 57.6; 34.5 ± 51.2 vs 52.9 ± 59.7; P < 0.001), age, previous endoscopic intervention, and immunosuppression. Multi-resistant (MR) strains were found in 11.3% of all samples and were associated with clinical and laboratory signs of cholangitis, previous intervention, and immunocompromised status. In subgroup analysis, strain-specific antibiotic therapy based on bile sampling was achieved in 56.3% (89/158) of the patients. In cases with a positive bile culture and available blood culture, blood cultures were positive in 29% of cases (36/124), and 94% (34/36) of blood cultures had microbial species identical to the bile cultures.Bactobilia and fungobilia can usually be detected by routine microbiological sampling, allowing optimized, strain-specific antibiotic treatment. Previous endoscopic intervention, clinical and laboratory signs of cholangitis, and age are independent risk factors. MR bacteria and fungi are an evolving problem in cholangitis, especially in immunocompromised patients., Competing Interests: The authors have no conflicts of interest to disclose.

Objective: Lethal sepsis occurs when an excessive inflammatory response evolves that cannot be controlled by physiologic anti-inflammatory mechanisms, such as the recently described cholinergic anti-inflammatory pathway. Here we studied whether the cholinergic anti-inflammatory pathway can be activated by pharmacologic cholinesterase inhibition in vivo., Design: Prospective, randomized laboratory investigation that used an established murine sepsis model., Setting: Research laboratory in a university hospital., Subjects: Female C57BL/6 mice., Interventions: Sepsis in mice was induced by cecal ligation and puncture. Animals were treated immediately with intraperitoneal injections of nicotine (400 microg/kg), physostigmine (80 microg/kg), neostigmine (80 microg/kg), or solvent three times daily for 3 days., Measurements and Main Results: Treatment with physostigmine significantly reduced lethality (p < or = .01) as efficiently as direct stimulation of the cholinergic anti-inflammatory pathway with nicotine (p < or = .05). Administration of cholinesterase inhibitors significantly down-regulated the binding activity of nuclear factor-kappaB (p < or = .05) and significantly reduced the concentration of circulating proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 (p < or = .001), and pulmonary neutrophil invasion (p < or = .05). Animals treated with the peripheral cholinesterase inhibitor neostigmine showed no difference compared with physostigmine-treated animals., Conclusions: Our results demonstrate that cholinesterase inhibitors can be used successfully in the treatment of sepsis in a murine model and may be of interest for clinical use.