Principles and requirements for stroke recovery science

The disappointing results in bench-to-bedside translation of neuroprotective strategies caused a certain shift in stroke research towards enhancing the endogenous recovery potential of the brain. One reason for this focus on recovery is the much wider time window for therapeutic interventions which is open for at least several months. Since recently two large clinical studies using d-amphetamine or fluoxetine, respectively, to enhance post-stroke neurological outcome failed again it is a good time for a critical reflection on principles and requirements for stroke recovery science. In principal, stroke recovery science deals with all events from the molecular up to the functional and behavioral level occurring after brain ischemia eventually ending up with any measurable improvement of various clinical parameters. A detailed knowledge of the spontaneously occurring post-ischemic regeneration processes is the indispensable prerequisite for any therapeutic approaches aiming to modify these responses to enhance post-stroke recovery. This review will briefly illuminate the molecular mechanisms of post-ischemic regeneration and the principle possibilities to foster post-stroke recovery. In this context, recent translational approaches are analyzed. Finally, the principal and specific requirements and pitfalls in stroke recovery research as well as potential explanations for translational failures will be discussed.     

Anterior vs Posterior Hippocampal Subfields in an Extended Psychosis Phenotype of Multidimensional Schizotypy in a Nonclinical Sample

Numerous studies have implicated involvement of the hippocampus in the etiology and expression of schizophrenia-spectrum psychopathology, and reduced hippocampal volume is one of the most robust brain abnormalities reported in schizophrenia. Recent studies indicate that early stages of schizophrenia are specifically characterized by reductions in anterior hippocampal volume; however, studies have not examined hippocampal volume reductions in subclinical schizotypy. The present study was the first to examine the associations of positive, negative, and disorganized schizotypy dimensions with hippocampal subfield volumes in a large sample (n = 195) of nonclinically ascertained young adults, phenotyped using the Multidimensional Schizotypy Scale (MSS). Hippocampal subfields were analyzed from high-resolution 3 Tesla structural magnetic resonance imaging scans testing anatomical models, including anterior vs posterior regions and the cornu ammonis (CA), dentate gyrus (DG), and subiculum subfields separately for the left and right hemispheres. We demonstrate differential spatial effects across anterior vs posterior hippocampus segments across different dimensions of the schizotypy risk phenotype. The interaction of negative and disorganized schizotypy robustly predicted left hemisphere volumetric reductions for the anterior and total hippocampus, and anterior CA and DG, and the largest reductions were seen in participants high in negative and disorganized schizotypy. These findings extend previous early psychosis studies and together with behavioral studies of hippocampal-related memory impairments provide the basis for a dimensional neurobiological hippocampal model of schizophrenia risk. Subtle hippocampal subfield volume reductions may be prevalent prior to the onset of detectable prodromal clinical symptoms of psychosis and play a role in the etiology and development of such conditions.     

Situating language in a minimal social context: how seeing a picture of the speaker’s face affects language comprehension

Natural use of language involves at least two individuals. Some studies have focused on the interaction between senders in communicative situations and how the knowledge about the speaker can bias language comprehension. However, the mere effect of a face as a social context on language processing remains unknown. In the present study, we used event-related potentials to investigate the semantic and morphosyntactic processing of speech in the presence of a photographic portrait of the speaker. In Experiment 1, we show that the N400, a component related to semantic comprehension, increased its amplitude when processed within this minimal social context compared to a scrambled face control condition. Hence, the semantic neural processing of speech is sensitive to the concomitant perception of a picture of the speaker’s face, even if irrelevant to the content of the sentences. Moreover, a late posterior negativity effect was found to the presentation of the speaker’s face compared to control stimuli. In contrast, in Experiment 2, we found that morphosyntactic processing, as reflected in left anterior negativity and P600 effects, is not notably affected by the presence of the speaker’s portrait. Overall, the present findings suggest that the mere presence of the speaker’s image seems to trigger a minimal communicative context, increasing processing resources for language comprehension at the semantic level.     

Secretory products from human adipocytes impair endothelial function via nuclear factor kappaB

Hyperplasia and hypertrophy of fat cells can be found in obesity, and increased adiposity is associated with endothelial dysfunction as an early event of atherosclerosis. However, it is unclear whether human adipocytes directly influence endothelial function. To study the crosstalk between fat and endothelial cells, human umbilical venous endothelial cells (HUVECs), and human coronary artery endothelial cells (HCAECs) were cultured in infranatants (Adipo) of primary differentiated human adipocytes. Interestingly, incubation of HUVECs and HCAECs with Adipo significantly increased monocyte adhesion 7.3 and 2.2-fold, respectively. VCAM-1, ICAM-1, and E-selectin in HUVECs were upregulated 3.9, 3.0, and 9.5-fold, respectively, under these conditions. Furthermore, Adipo significantly stimulated NFkappaB activity 1.9-fold. The NFkappaB inhibitor MG-132 and heat inactivation significantly reversed Adipo-stimulated monocyte adhesion. TNFalpha-neutralizing antibodies partly reversed Adipo-induced monocyte adhesion. In contrast, thiazolidinedione-pretreatment of human adipocytes did not alter the effects of Adipo. Adipo did not show cytotoxic effects. Taken together, we demonstrate that endothelial dysfunction is induced by adipocyte-secreted factors via NFkappaB partly dependent on TNFalpha.     

Opioide bei chronischem Arthroseschmerz

Background

The efficacy, tolerability and safety of opioid therapy in chronic osteoarthritis (OA) pain is under debate. We updated a Cochrane systematic review on the efficacy and safety of opioids in chronic OA pain published in 2009.

Methods

We screened MEDLINE, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) up until October 2013, as well as reference sections of original studies and systematic reviews of randomized controlled trials (RCTs) of opioids in chronic osteoarthritis (OA) pain. We included double-blind randomized placebo-controlled studies lasting ≥?4 weeks. Using a random effects model, absolute risk differences (RD) were calculated for categorical data and standardized mean differences (SMD) for continuous variables.

Results

We included 20 RCTs with 33 treatment arms and 8545 participants. Median study duration was 12 (4–24) weeks. Oxycodone and tramadol were each tested in six studies; buprenorphine, hydromorphone, morphine and tapentadol each in two studies and codeine, fentanyl and oxymorphone in one study each. Results are reported with 95?% confidence intervals (CIs). Opioids were superior to placebo in reducing pain intensity (SMD ??0.22 [??0.28, ??0.17], p?<?0.00001; 16 studies with 6743 participants). Opioids were not superior to placebo in 50?% pain reduction (RD ??0.00 [??0.07, 0.07], p?=?0.96; two studies with 2684 participants). Opioids were superior to placebo in terms of reports of much or very much global improvement (RD 0.13 [0.05, 0.21], p?=?0.002; three studies with 2251 participants). Opioids were superior to placebo in improving physical functioning (SMD ??0.22 [??0.28, ??0.17], p?<?0.00001; 14 studies with 5887 participants). Patients dropped out more frequently with opioids than with placebo (RD 0.17 [0.14, 0.21], p?<?0.00001; 15 studies with 6834 participants; number needed to harm 5 [4–6]. There was no significant difference between opioids and placebo in the frequency of serious adverse events (SAE) or deaths over the respective observation periods.

Conclusion

Opioids were superior to placebo in terms of efficacy and inferior in terms of tolerability. The effect sizes of average reduction in pain intensity and physical disability were small. Opioids and placebo did not differ in terms of safety. The conclusion on the safety of opioids compared to placebo is limited by the low number of SAE and deaths. Short-term opioid therapy may be considered in selected chronic OA pain patients. No current evidence-based guideline recommends opioids as first-line treatment option for chronic OA pain. To provide superior evidence for future treatment guidelines, RCTs must directly compare existing pharmacological and nonpharmacological therapies and administer these in various combinations and sequences.The English full-text version of this article is freely available at SpringerLink (under “Supplemental”).

     

Randomized controlled trial comparing Moviprep® and Phosphoral® as bowel cleansing agents in patients undergoing colonoscopy

Background

Introducing colonoscopy as part of colorectal cancer screening on a national level, we aimed at evaluating the efficacy of the two most common bowel cleansing agents, Moviprep^® and Phosphoral^®. Secondly, we evaluated the benefit for the patient and society in terms of sick leave and discomfort.

Methods

In a single-blinded randomized equivalence trial, Phosphoral^® (NaP) was compared with Moviprep^® (2 l polyethylene glycol + ascorbic acid) in patients undergoing colonoscopy due to suspicion of cancer. Patients filled out questionnaires concerning stool consistency, discomfort and number of sick days due to bowel cleansing. Blinded colonoscopists estimated the efficiency of the cleansing using the validated Harefield Cleansing Scale.

Results

Two hundred and sixty-six patients were included 250 of whom underwent full colonoscopy. There was no difference in the percentage of acceptable bowel cleansings in the two groups; however, a significantly higher number of A scores were observed in the Moviprep^® group (p = 0.028). We found no correlation between stool consistency and outcome of the cleansing and no difference in subjective discomfort during cleansing. Vomiting during cleansing occurred more often in the Phosphoral^® group (p = 0.002). There was a trend toward a smaller number of sick days in patients who used Moviprep^® compared with Phosphoral^®.

Conclusions

Moviprep^® and Phosphoral^® provided equally efficient bowel cleansing in 90 % of patients, but Moviprep^® provided a higher quality of cleansings graded as successful. The two agents were equally tolerated, and no difference was found in the related number of sick days.     

Non-fluoroscopic catheter visualization using MediGuide™ technology: experience from the first 600 procedures

A novel cardiovascular navigation system known as MediGuide? (MG) which allows non-fluoroscopic catheter tracking over a background of pre-recorded cine loops was recently introduced. This system allows significant reduction of fluoroscopy exposure which is one of the potentially harmful aspects of today's electrophysiological procedures such as ablations or device implantations. We provide a summary of recently published studies related to this new technological platform and describe our experience from the first 600 MG procedures at our institution. After reviewing the currently available publications in the field of MG-supported EP procedures, we describe the workflows for (1) ablation of supraventricular tachycardia (SVT), atrial fibrillation (AF), and ventricular tachycardia using MG-enabled diagnostic and ablation catheters, as well as (2) implant of cardiac resynchronization therapy (CRT) devices using sensor-equipped delivery tools including sheaths, sub-selectors, and guidewires. As shown in several studies [5–9], MG procedures resulted in similar efficacy as conventional cases but with a significant reduction in fluoroscopy time and dose. In particular, for SVT ablations, the median fluoroscopy time using the MG technology was 0.5?±?1.4 min compared to 10.2?±?9.6 min in conventional fluoroscopic settings. Similar reductions were demonstrated for AF ablation procedures from 25 min in conventional settings with electroanatomical mapping systems and live x-ray to 4.6 min with the addition of the MG technology. Recently, it was demonstrated that the application of MG for CRT device implants could successfully result in a median fluoroscopy time of 2.6 min for LV lead deployment. In summary, the first measurable clinical impact of the MG technology on a daily clinical routine is the reduction of fluoroscopy time and radiation exposure for various EP indications. These beneficial effects were achieved without negative consequences on procedural efficacy, complications, or time in more than 600 EP procedures.     

Motivation for and adherence to growth hormone replacement therapy in adults with hypopituitarism: the patients‘ perspective

Pituitary - While reasons for non-adherence in children requiring growth hormone (GH) replacement (GH-Rx) are well researched, few studies have investigated adherence in adult GH deficient...     

Functional short- and long-term effects of nasal CPAP with and without humidification on the ciliary function of the nasal respiratory epithelium

Purpose

Continuous positive airway pressure (CPAP) is the gold standard in the treatment of obstructive sleep apnea (OSA), but its impact on ciliary function is unclear to date. Furthermore, CPAP is associated with numerous side effects related to the nose and upper airway. Humidified CPAP is used to relieve these symptoms, but again, little is known regarding its effect on ciliary function of the nasal respiratory epithelium.

Methods

In this prospective, randomized, crossover trial, 31 patients with OSA (AHI >15/h) were randomized to two treatment arms: nasal continuous positive airway pressure (nCPAP) with humidification or nCPAP without humidification for one night in each modality to assess short-term effects of ciliary beat frequency (CBF) and mucus transport time (MTT) and consecutively for 8 weeks in each modality to assess long-term effects in a crossover fashion.

Results

The baseline CBF was 4.8?±?0.6 Hz, and baseline MTT was 540?±?221 s. After one night of CPAP with and without humidification, ciliary function increased moderately yet with statistical significance (p <0.05). The short-term groups with and without humidification did not differ statistically significant. Regarding long-term effects of CPAP, a statistically significant increase in ciliary function above the baseline level and above the short-term level was shown without humidification (7.2?±?0.4 Hz; 402?±?176 s; p <0.01). The increase above baseline level was even more pronounced with humidification (9.3?±?0.7 Hz; 313?±?95 s; p <0.01). There was a statistically significant difference between both groups at long-term assessment with regard to CBF (p <0.01).

Conclusions

Independent of airway humidification, nCPAP has moderate effects on short-term ciliary function of the nasal respiratory epithelium. However, a significant increase in ciliary function—both in terms of an increased CBF and a decreased MTT—was detected after long-term use. The effect was more pronounced when humidification was used during nCPAP.