Accuracy of MRI-guided Versus Systematic Prostate Biopsy in Patients Under Active Surveillance: A Systematic Review and Meta-analysis

This meta-analysis focuses on the accuracy of upgrading to clinically significant prostate cancer (PCa) by multiparametric magnetic resonance imaging-targeted biopsy (MRI-TB) versus systematic biopsy (SB). We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Literatura Latino Americana em Ciências da Saúde databases through January 2020 for comparative, retrospective/prospective, paired-cohort, and randomized clinical trials with paired comparisons. The population consisted of patients with low-risk PCa in active surveillance with at least 1 index lesion on imaging. We evaluated the quality of evidence by using the Quality Assessment of Diagnostic Accuracy Studies-2 score. Group comparisons considered the differences between the area under the curve summary receiver operating characteristic curve in a 2-tailed method. We also compared the positive predictive value of the best single method (MRI-TB or SB) and the referral study test (combined biopsy, a combination of MRI-TB and SB). The meta-analysis included 6 studies enrolling 741 patients. The pooled sensitivity for the 2 groups was 0.79 (95% confidence interval, 0.74-0.83; I² = 75%) and 0.67 (95% confidence interval, 0.63-0.74; I² = 55.4%), respectively. The area under the curve for the MRI-TB and SB groups were 0.99 and 0.92 (P < .001), respectively. The positive predictive value for the MRI-TB and combined biopsy groups were similar. The accumulated evidence suggests better results for MRI-TB compared with SB. Therefore, use of MRI-TB alone may be preferable in patients in active surveillance harboring low-risk PCa.     

Conjugation pathways in liver disease.

1. The activities of microsomal glucuronyltransferase and thiomethyltransferase, and those of cytosolic sulphotransferase, acetyltransferase, glutathione transferase and thiomethyltransferase were measured in abnormal (cirrhosis and chronic hepatitis) and normal livers. 2. Glucuronyltransferase and sulphotransferase were investigated with 2-naphthol and ethinyloestradiol as substrates. p-Aminobenzoic acid, benzo(a)pyrene-4,5-epoxide and 2-mercaptoethanol were the substrates of acetyltransferase, glutathione transferase and thiomethyltransferase, respectively. 3. Enzyme activities are expressed as nmol min-1 incubation mg-1 protein and the averages (+/- s.d.) are given. With 2-naphthol as substrate, the glucuronyltransferase activity was 6.55 +/- 4.10 (abnormal liver, n = 33) and 7.81 +/- 4.02 (normal liver, n = 26) (NS); whereas sulphotransferase activity was 0.28 +/- 0.18 (abnormal liver, n = 35) and 0.68 +/- 0.43 (normal liver, n = 26) (P less than 0.01). Glucuronyltransferase activity towards ethinyloestradiol was 102.5 +/- 56.9 (abnormal liver, n = 30) and 107 +/- 59.9 (normal liver, n = 26) (NS), whereas sulphotransferase activity was 57.2 +/- 36.0 (abnormal liver, n = 35) and 122 +/- 67.6 (normal liver, n = 28) (P less than 0.01). Acetyltransferase activity was 0.84 +/- 0.83 (abnormal liver, n = 35) and 3.84 +/- 1.65 (normal liver, n = 26) (P less than 0.01). Glutathione transferase activity was 0.83 +/- 0.68 (abnormal liver, n = 35) and 2.90 +/- 1.59 (normal liver, n = 25) (P less than 0.01) and thiomethyltransferase activity was 1.00 +/- 0.69 (abnormal liver, n = 34) and 3.99 +/- 1.49 (normal liver, n = 25) (P less than 0.01). 4. Liver disease lowers the activities towards the substrates studied of sulphotransferase, acetyltransferase, glutathionetransferase and thiomethyltransferase but not that of glucuronyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial electrophysiologic properties in paroxysmal atrial fibrillation. Study conducted with the stimulation of 5 atrial sites

Programmed atrial stimulation at five atrial sites was performed to evaluate electrophysiologic atrial properties in 17 control patients (14 M, 3F, mean age 61 +/- 9 years) (Group A) and in 18 patients with paroxysmal atrial fibrillation (13 M, 5 F, mean age 61 +/- 5 years) (Group B) with normal sinus node function. The mean value of the P wave duration was similar in both groups. Programmed atrial stimulation was performed at five atrial sites: high, medium and low lateral wall, and high and low medial wall. We evaluated the following parameters: A) local conduction delay measured at the functional refractory period as the difference between A1-A2 and S1-S2 intervals; B) widening of local electrogram measured at the functional refractory period as the difference between A1-A2 interval measured at the end of each local electrogram and A1-A2 interval measured at the beginning of each local electrogram. We evaluated the mean and the maximum value of the two above-mentioned parameters; C) dispersion of effective refractory period and functional refractory period, determined as the longest minus the shortest refractory period from the range of refractory periods measured in each patient; D) the mean of effective refractory periods and functional refractory periods observed at five atrial sites. Mean and maximum local conduction delay, mean effective and functional refractory periods did not present significant differences in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Stable preference for high ethanol concentrations after ethanol deprivation in Sardinian alcohol-preferring (sP) rats.

Results of a recent study have demonstrated that exposure to multiple ethanol concentrations and repeated ethanol deprivation periods in Indiana ethanol-preferring (P) rats resulted in the development of an alcohol deprivation effect (ADE; the temporary increase in voluntary ethanol intake after a period of deprivation from ethanol) characterized by consumption of intoxicating amounts of ethanol. The current study was designed to possibly extend these results to Sardinian alcohol-preferring (sP) rats, generated with the same selective program previously used for P rats. To this aim, ethanol-naive sP rats were exposed initially to the home cage four-bottle choice [10%, 20%, and 30% (vol./vol.) ethanol solutions and water] for eight consecutive weeks. Subsequently, rats were divided into two groups: The first group had continuous access to the four-bottle regimen (nondeprived rats), and the second group was exposed to five cycles of 14-day periods of deprivation from ethanol and 14-day periods of reexposure to the four-bottle regimen. An ADE developed after each deprivation period. However, the extra intake of ethanol was limited to the first hour of each reaccess period. Magnitude of ADE did not change with repeated periods of deprivation. However, a shift in preference toward the two highest concentrations of ethanol solutions was evident from the first reexposure to ethanol and was maintained throughout the study. These results provide further evidence on the heterogeneity of ethanol-drinking behavior among rat lines selectively bred for high ethanol preference and consumption.     

Treatment of Status Epilepticus in Adults: Guidelines of the Italian League Against Epilepsy

Summary:  Status epilepticus (SE) is a medical emergency which can lead to significant morbidity and mortality and requires prompt diagnosis and treatment. SE is differentiated into generalized or partial SE on the basis of its electro-clinical manifestations. The guidelines for the management of SE produced by the Italian League against Epilepsy also distinguish three different stages of SE (initial, established and refractory), based on time elapsed since the onset of the condition and responsiveness to previously administered drugs. Treatment should be started as soon as possible, particularly in generalized convulsive SE, and should include general support measures, drugs to suppress epileptic activity and, whenever possible, treatments aimed at relieving the underlying (causative) condition. Benzodiazepines are the first line antiepileptic agents, and i.v. lorazepam is generally preferred because it is associated with a lower risk of early relapses. If benzodiazepines fail to control seizures, i.v. phenytoin is usually indicated, though i.v. phenobarbital or i.v. valproate may also be considered. Refractory SE requires admission to an intensive care unit (ICU) to allow adequate monitoring and support of respiratory, metabolic and hemodynamic functions and cerebral electrical activity. In refractory SE, general anesthesia may be required. Propofol and thiopental represent first line agents in this setting, after careful assessment of potential risks and benefits.     

Chronic peritoneal dialysis in paediatrics: Experience of a national registry

The results of the first 3 year' collaboration of the Italian Registry of Paediatric Chronic Peritoneal Dialysis (CPD) (1986–1988) are presented. This Registry acquired data on the majority of the paediatric patients treated with CPD in Italy, thus providing a national picture in a field where few nationwide surveys are available. Patients of less than 15 years of age at the start of dialysis were enrolled and clinical data collected until the age of 19 years. The number of nephrological paediatric centres participating in the Registry increased from 7 in 1986 to 11 in 1988. The total number of patients on CPD was 70 and the percentage of dialysed children treated with CPD ranged from 40.2% to 43.6%. Data on 89 peritoneal catheters were collected: during 1417 dialysis-months 70 catheter-related complications were observed (1:20.8 dialysis-months); actuarial catheter survival was 92.7% at 6 months, 84.8% at 1 year and 68.8% at 2 years. The incidence of peritonitis changed from 1 episode every 10.9 patient-months in 1986 to 1 every 19.8 in 1988. Abdominal hernias were the other main clinical complication observed. The survival of patients was 92.5% at 3 years, while the technique survival at the same time was 84%.     

When poor solubility becomes an issue: From early stage to proof of concept

Drug absorption, sufficient and reproducible bioavailability and/or pharmacokinetic profile in humans are recognized today as one of the major challenges in oral delivery of new drug substances. The issue arose especially when drug discovery and medicinal chemistry moved from wet chemistry to combinatorial chemistry and high throughput screening in the mid-1990s. Taking into account the drug product development times of 8–12 years, the apparent R&D productivity gap as determined by the number of products in late stage clinical development today, is the result of the drug discovery and formulation development in the late 1990s, which were the early and enthusiastic times of the combinatorial chemistry and high throughput screening. In parallel to implementation of these new technologies, tremendous knowledge has been accumulated on biological factors like transporters, metabolizing enzymes and efflux systems as well as on the physicochemical characteristics of the drug substances like crystal structures and salt formation impacting oral bioavailability. Research tools and technologies have been, are and will be developed to assess the impact of these factors on drug absorption for the new chemical entities.

The conference focused specifically on the impact of compounds with poor solubility on analytical evaluation, prediction of oral absorption, substance selection, material and formulation strategies and development. The existing tools and technologies, their potential utilization throughout the drug development process and the directions for further research to overcome existing gaps and influence these drug characteristics were discussed in detail.