Overall and disease-specific survival of sinonasal adenoid cystic carcinoma: a systematic review and meta-analysis.

This meta-analysis aims to investigate the outcome of sinonasal adenoid cystic carcinoma (snAdCC). We followed PRISMA guidelines and included studies reporting 5-year overall survival (OS) rates for snAdCC. Eligible studies were identified through a literature search and assessed using JBI critical appraisal checklist. A total of 17 studies were included comprising 2259 patients (mean age: 58.1 years, 52.7% female, 47.3% male). The meta-analysis demonstrated that the 5-year OS, 10-year OS, and 5-year disease-free survival (DFS) were 68%, 40%, and 47.2%, respectively. Descriptive statistics on study level showed high rates of locally advanced tumor stages at diagnosis: 23% cT3, 53% cT4, 3.4% N+, and 4.2% M+. 29.7% of the tumors were in the nasal cavity, 67.6% in the paranasal sinuses. The maxillary, ethmoid, sphenoid, and frontal sinus were affected in 50.9%, 7.2%, 4%, and 0.5%, of cases. A combination of surgery and radiotherapy was used in 45.4% of the patients and 19.3% of patients received surgery only. In conclusion, these findings emphasize the significance of thorough surveillance for individuals with snAdCC to identify any potential recurrence or progression of the disease.

Validity of outcome measures used in randomized clinical trials and observational studies in degenerative lumbar spinal stenosis.

It is unclear whether outcome measures used in degenerative lumbar spinal stenosis (DLSS) have been validated for this condition. Cross-sectional analysis of studies for DLSS included in systematic reviews (SA) and meta-analyses (MA) indexed in the Cochrane Library. We extracted all outcome measures for pain and disability. We assessed whether the studies provided external references for the validity of the outcome measures and the quality of the validation studies. Out of 20 SA/MA, 95 primary studies used 242 outcome measures for pain and/or disability. Most commonly used were the VAS (n = 69), the Oswestry Disability Index (n = 53) and the Zurich Claudication Questionnaire (n = 22). Although validation references were provided in 45 (47.3%) primary studies, only 14 validation studies for 9 measures (disability n = 7, pain and disability combined n = 2) were specifically validated in a DLSS population. The quality of the validation studies was mainly poor. The Zurich Claudication Questionnaire was the only disease specific tool with adequate validation for assessing treatment response in DLSS. To compare results from clinical studies, outcome measures need to be validated in a disease specific population. The quality of validation studies need to be improved and the validity in studies adequately cited.

Association between depression and anxiety on symptom and function after surgery for lumbar spinal stenosis.

Evidence on the role of depression and anxiety in patients undergoing surgical treatment for symptomatic degenerative lumbar spinal stenosis (DLSS) is conflicting. We aimed to assess the association between depression and anxiety with symptoms and function in patients undergoing surgery for DLSS. Included were patients with symptomatic DLSS participating in a prospective multicentre cohort study who underwent surgery and completed the 24-month follow-up. We used the hospital anxiety and depression scale (HADS) to assess depression/anxiety. We used mixed-effects models to quantify the impact on the primary outcome change in the spinal stenosis measure (SSM) symptoms/function subscale from baseline to 12- and 24-months. Logistic regression analysis was used to quantify the odds of the SSM to reach a minimal clinically important difference (MCID) at 24 months follow-up. The robustness of the results in the presence of unmeasured confounding was quantified using a benchmarking method based on a multiple linear model. Out of 401 patients 72 (17.95%) were depressed and 80 anxious (19.05%). Depression was associated with more symptoms (ß = 0.36, 95% confidence interval (CI) 0.20 to 0.51, p < 0.001) and worse function (ß = 0.37, 95% CI 0.24 to 0.50, p < 0.001) at 12- and 24-months. Only the association between baseline depression and SSM symptoms/function was robust at 12 and 24 months. There was no evidence for baseline depression/anxiety decreasing odds for a MCID in SSM symptoms and function over time. In patients undergoing surgery for symptomatic DLSS, preoperative depression but not anxiety was associated with more severe symptoms and disability at 12 and 24 months.

Serial assessment of somatic and cardiovascular development in patients with single ventricle undergoing Fontan procedure.

BACKGROUND: The palliation of patients with single ventricle (SV) undergoing Fontan procedure led to improved long-term survival but is still limited due to cardiovascular complications. The aim of this study was to describe the somatic and cardiovascular development of Fontan patients until adolescence and to identify determining factors. METHODS: We retrospectively assessed somatic growth, vascular growth of pulmonary arteries, and cardiac growth of the SV and systemic semilunar valve from 0 to 16 years of age using transthoracic echocardiography. The Doppler inflow pattern of the atrioventricular valve was quantified by E-, A-wave and E/A ratio. All data were converted to z-scores and analyzed using linear mixed effect models to identify associations with age at Fontan procedure, gender, and ventricular morphology. RESULTS: 134 patients undergoing Fontan procedure at a median age of 2.4 (IQR 2.12 to 2.8) years were analyzed. A catch-up of somatic growth after Fontan procedure until school age was found, with lower body height and weight z-scores in male patients and patients with systemic right ventricles. An early time of Fontan procedure was favorable for somatic growth, but not for vascular growth. Cardiac development indicated a decrease of SV end-diastolic diameter z-score until adolescence. Despite a trend towards normalization, E-wave and E/A ratio z-scores were diminished over the entire period. CONCLUSIONS: There is a catch-up growth of somatic, vascular and cardiac parameters after Fontan procedure, which in our cohort depends on the time of Fontan procedure, ventricular morphology, and gender. Beside other factors, diastolic function of the SV remains altered.

Association of perinatal risk factors with neurological outcome in neonates with hypoxic ischemic encephalopathy.

OBJECTIVE: Neonates exposed to perinatal insults typically present with hypoxic ischemic encephalopathy (HIE). The aim of our study was to analyze the association between known risk factors for HIE and the severity of encephalopathy after birth and neurological outcome in neonates during the first 4 d of life. METHODS: Retrospective cohort study including 174 neonates registered between 2011 and 2013 in the National Asphyxia and Cooling Register of Switzerland. RESULTS: None of the studied perinatal risk factors is associated with the severity of encephalopathy after birth. Fetal distress during labor (OR, 2.06; 95% CI, 1.02-4.25, p = .049) and neonatal head circumference (HC) above 10th percentile (p10) at birth (OR, 1.33; 95% CI, 1.05-1.69, p = .02) were associated with neurological benefit in the univariate analysis. Fetal distress on maternal admission for delivery was the only risk factor for neurological harm in the univariate (OR, 0.26; 95% CI, 0.12-0.57, p < .01) and the multivariate analysis (OR, 0.15; 95% CI, 0.04-0.67, p = .013). We identified two different patient scenarios: the probability for neurological benefit during the first 4 d of life was only 20% in neonates with the combination of all the following risk factors (gestational age >41 weeks, chorioamnionitis, fetal distress on maternal admission for delivery, fetal distress during labor, sentinel events during labor, HC below 10th percentile), whereas in the absence of these risk factors the probability for neurological benefit increased to 80%. CONCLUSIONS: We identified a constellation of risk factors that influence neurological outcome in neonates with HIE during the first 4 d of life. These findings may help clinicians to counsel parents during the early neonatal period. (ClinicalTrials.gov NCT02800018).

Depression is independently associated with increased length of stay and readmissions in multimorbid inpatients.

BACKGROUND: Little is known about the impact of depression across a broad range of multimorbid patients hospitalized for reasons other than depression. The objective of the study was to investigate in a large sample of multimorbid inpatients whether ancillary depression is associated with increased length of stay (LOS) and readmissions, two important clinical outcomes with implications for healthcare utilization and costs. METHODS: We retrospectively analyzed a cohort of 253,009 multimorbid inpatients aged ≥18 at an academic medical center, 8/2009-8/2017. PRIMARY OUTCOME: LOS. SECONDARY OUTCOMES: LOS related to different main diagnoses, readmissions within 1, 3, 6, 12, and 24-months after discharge. RESULTS: Multivariable linear regression showed 24% longer LOS in patients with ancillary depression (1.24; 95% confidence interval [CI]: 1.22, 1.25). Females stayed 22% longer (1.22; 95% CI: 1.20, 1.25), males 24% (1.24; 95% CI: 1.22, 1.27). We identified 16 main diagnosis clusters in which ancillary depression was associated with significant LOS increases, with associations being strongest for "Failure and rejection of transplanted organs and tissues", "Other noninfective gastroenteritis and colitis", and "Other soft tissue disorders, not elsewhere classified". Multivariable logistic and Poisson regression showed independent associations of ancillary depression with increased readmission odds and frequencies at 1, 3, 6, 12, and 24 months. CONCLUSIONS: Ancillary depression was independently associated with increased LOS and more readmissions across a broad range of multimorbid inpatients.

Relationship between temperature variability and brain injury on magnetic resonance imaging in cooled newborn infants after perinatal asphyxia.

OBJECTIVE: The objective of the study was whether temperature management during therapeutic hypothermia correlates with the severity of brain injury assessed on magnetic resonance imaging in term infants with hypoxic-ischemic encephalopathy. STUDY DESIGN: Prospectively collected register data from the National Asphyxia and Cooling Register of Switzerland were analyzed. RESULT: Fifty-five newborn infants were cooled for 72 h with a target temperature range of 33 to 34 °C. Individual temperature variability (odds ratio (OR) 40.17 (95% confidence interval (CI) 1.37 to 1037.67)) and percentage of temperatures within the target range (OR 0.95 (95% CI 0.90 to 0.98)) were associated with the severity of brain injury seen on magnetic resonance imaging (MRI). Neither the percentage of measured temperatures above (OR 1.08 (95% CI 0.96 to 1.21)) nor below (OR 0.99 (95% CI 0.92 to 1.07) the target range was associated with the severity of brain injury seen on MRI. CONCLUSION: In a national perinatal asphyxia cohort, temperature variability and percentage of temperatures within the target temperature range were associated with the severity of brain injury.

Success of 6-mm Implants with Single-Tooth Restorations: A 3-year Randomized Controlled Clinical Trial.

The aim of the study was to test whether implants of 6 mm in length perform equally well as 10-mm implants in terms of survival and marginal bone-level changes when supporting single crowns. Patients with a posterior single-tooth gap were randomly allocated to either the placement of a 6-mm (test) or 10-mm implant (control). The treatment protocol allowed for internal sinus lift but not for lateral bone augmentation. After a healing period of 10 wk, implants were loaded with screw-retained single crowns. Survival rates, number of pockets ≥5 mm, and bleeding-on-probing were assessed clinically. The change of marginal bone level and crown-to-implant ratios were analyzed by 2 examiners. Longitudinal intragroup analyses for marginal bone levels were performed applying the Wilcoxon signed rank test. Intergroup differences at baseline and at 3 y were compared using the Mann-Whitney U test. The effect of implant length and crown-to-implant ratio on changes of marginal bone level also was determined. Of 94 implants placed (47 test and 47 control), 78 implants (40 test and 38 control) were available for follow-up examination at 3 y of loading. One test implant was lost during the second year. Hence, implant survival was not significantly different between the 2 groups after 3 y (98% test; 100% control). We found no significant change in the crestal bone level from baseline to 3 y for test and control implants with -0.19 ± 0.62 mm and -0.33 ± 0.71 mm, respectively. The intergroup difference was not significant. Crown-to-implant ratios were not associated with a statistically significant difference in marginal bone loss. However, the number of sites with pockets ≥5 mm was significantly higher in the test group. Based on the 3-y assessment, the use of 6-mm implants can be considered a viable option when reconstructing posterior single tooth gaps (German Clinical Trials Registry: DRKS00006290).

Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2).

BACKGROUND: Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown. PATIENTS AND METHODS: A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively. Inclusion in the study required a predefined clinical data set, a central neuro-radiological or histopathological confirmation of metastatic CNS involvement and central assessment of HER2 by immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition, expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by IHC. RESULTS: One hundred patients fulfilled the inclusion criteria. The population's median age was 59 years (interquartile range: 54-68), of which 85 (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin. HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from initial diagnosis to the development of brain metastases (BMets) or leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss of expression in at least one DNA MMR proteins in 6%. CONCLUSIONS: The proportion of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and CNS involvement was higher than expected. The impact of anti-HER2 therapies should be studied prospectively.

A multifaceted intervention: no increase in general practitioners' competence to diagnose skin cancer (minSKIN) - randomized controlled trial.

BACKGROUND: General practitioners (GPs) play crucial roles in early detection of skin cancer. A pilot-study found a positive short-term effect of a 1-day dermatologic education programme on GPs' diagnostic competence. OBJECTIVE: To determine effects of a multifaceted intervention, including technical equipment and continuing feedback by a dermatologist, on GPs' diagnostic skills regarding skin cancer. METHODS: Randomized controlled trial with 78 GPs of the Canton of Zurich, Switzerland. INTERVENTION: GPs in intervention group received a 1-day training, a Lumio (magnifying glass with polarized light, 3Gen), a Nikon digital camera and - during 1 year - feedback on skin lesion pictures sent to the dermatologist. GPs in control group only received the 1-day training. PRIMARY OUTCOME: structured assessment of GP's diagnostic skills in correctly diagnosing images of skin lesions regarding skin cancer. At baseline prior to intervention (T0), after the full-day training course in both groups (T1), and after 1 year of continuing feedback (T2) to the intervention group. MEASURES: Non-parametric unpaired (Wilcoxon-Mann-Whitney) tests were used to compare numbers of correctly classified skin lesions between both groups at T2 and for the change between T1 and T2. RESULTS: At T0, both groups classified a median of 23 skin lesions of the 36 images correctly. This value rose to 28 for both groups at T1 and fell to 24 for both groups at T2. No difference between control and intervention group at T2. Furthermore, we compared differences in the sum scores per GP between T1 and T2 for each group. Also in this comparison, no difference between control and intervention group was found. CONCLUSION AND RELEVANCE: No long-term effect of the multifaceted intervention was found on the competence to diagnose skin cancer by GPs. The positive short-term effect of the 1-day dermatologic education programme did not persist over 12 months.

Antibiotic-impregnated versus silver-bearing external ventricular drainage catheters: preliminary results in a randomized controlled trial.

BACKGROUND: Evaluation of antibiotic-impregnated (AI) and ionized silver particle coated external ventricular drainage catheters (EVD) in patients with subarachnoid (SAH) or intracranial hemorrhage (ICH). METHODS: Between February 2011 and June 2012, 40 patients with acute hydrocephalus due to SAH, ICH or intraventricular hemorrhage were enrolled in a prospective, randomized, mono-center pilot study. Primary endpoints were defined as: number of events of cerebrospinal fluid (CSF) infections. Secondary endpoints were defined as: neurosurgical complications following the placement of the EVD, number of revisions of EVD catheters, and cost effectiveness. RESULTS: Sixty-one EVD placements in 40 patients, 32 antibiotic-coated (Bactiseal(®)), 29 silver-bearing catheters (VentriGuard(®)), have been performed. Confirmed or high suspicion of CSF infections occurred in 11 out of 61 events (confirmed infection: p = 0.71, probable infection: p = 0.90). Revisions of EVD were needed in 13 cases (22 %) due to CSF infection, dysfunction, impaired healing, or malplacement (p = 0.37). CONCLUSION: Regarding CSF infection rate and dysfunction, no statistical significant differences between the two EVD catheters Bactiseal(®) versus VentriGuard(®) were found. The silver-bearing catheter might offer a safe and cost-conscious alternative to the AI catheter.

Fatigue and excessive daytime sleepiness in idiopathic Parkinson's disease differently correlate with motor symptoms, depression and dopaminergic treatment.

BACKGROUND AND PURPOSE: A comprehensive study of both fatigue and excessive daytime sleepiness (EDS) in association with Parkinson's disease (PD)-related symptoms and treatment has not been performed yet. To assess the frequency and severity of fatigue and EDS in patients with idiopathic PD and to study their relation to motor and non-motor symptoms and dopaminergic treatment. METHODS: We prospectively assessed Fatigue Severity Scale (FSS) scores, Epworth Sleepiness Scale (ESS) scores, Beck Depression Inventory (BDI) scores, severity (Unified PD Rating Scale, UPDRS, part III; Hoehn & Yahr staging) and duration of the disease, and the current dopaminergic treatment in 88 consecutive patients with idiopathic PD. RESULTS: Fatigue was found in 52 (59%), EDS in 42 (48%), and both complaints in 31 (35%) patients. Fatigued patients had higher UPDRS III scores (23.5 ± 11.1 vs. 18.6 ± 7.6, P = 0.03), higher Hoehn & Yahr staging (2.4 ± 0.9 vs. 2.1 ± 0.7, P = 0.03), and higher BDI scores (13.4 ± 7.1 vs. 9.1 ± 5.8, P = 0.004) than non-fatigued patients. In contrast, UPDRS III, Hoehn & Yahr, and BDI scores did not differ between patients with or without EDS. However, the type of dopaminergic treatment (levodopa monotherapy versus combination of levodopa/dopamine agonists) was associated with significant differences in ESS (8.5 ± 5.2 vs. 10.8 ± 4.3, P = 0.04), but not FSS scores (4.1 ± 1.5 vs. 4.3 ± 1.5, P = 0.55). Disease duration correlated with ESS scores (r = 0.32, P = 0.003), but not with FSS scores (r = -0.02, P = 0.82). CONCLUSIONS: In PD, there is a significant overlap of fatigue and EDS, but the two symptoms are differently correlated with the severity of motor symptoms, disease duration, depression, and dopaminergic treatment.

Magnetic resonance imaging as a surrogate outcome for multiple sclerosis relapses.

BACKGROUND: Magnetic resonance imaging (MRI) of lesions in the brain may be the best current candidate for a surrogate biological marker of clinical outcomes in relapsing remitting multiple sclerosis (MS), based on its role as an objective indicator of disease pathology. No biological surrogate marker has yet been validated for MS clinical outcomes. OBJECTIVE: The objective of this study was to use a multi-phased study to determine if a valid surrogate relationship could be demonstrated between counts of contrast enhancing lesions (CELs) and occurrence of relapses in MS. METHODS: We examined correlations for the concurrent and predictive relationship between CELs over 6 months and MS relapses over the same 6 months and an additional 6 months (total: 12 months), using available data on untreated patients from a large clinical trial and natural history database. RESULTS: Concurrent and predictive correlations were inadequate to justify continuation of this study to the planned additional phases required to demonstrate a surrogate relationship between CELs and MS relapses. CONCLUSIONS: Confidence intervals for correlations between CELs and MS relapses exclude the possibility that CELs can be a good surrogate for relapses over the time scales we investigated. Further exploration of surrogacy between MRI measures and MS clinical outcomes may require improved datasets, the development of MRI techniques that couple better to clinical disease, and the ability to test a wide range of imaging- and clinically-based hypotheses for surrogacy.

Interpretation of treatment changes in 6-minute walk distance in patients with COPD.

There is uncertainty about the interpretation of changes in the 6-min walk distance (6MWD) in chronic obstructive pulmonary disease (COPD) patients and whether the minimal important difference (MID) for this useful outcome measure exists. Data were used from nine trials enrolling a wide spectrum of COPD patients with 6MWD at baseline and follow-up and used to determine threshold values for important changes in 6MWD using three distribution-based methods. Anchor-based methods to determine a MID were also evaluated. Data were included of 460 COPD patients with a mean+/-sd forced expiratory volume in one second (FEV(1)) of 39.2+/-14.1% predicted and 6MWD of 361+/-112 m at baseline. Threshold values for important effects in 6MWD were between 29 and 42 m, respectively, using the empirical rule effect size and the standardised response mean. The threshold value was 35 m (95% confidence interval 30-42 m) based on the standard error of measurement. Correlations of 6MWD with patient-reported anchors were too low to provide meaningful MID estimates. 6-min walk distance should change by approximately 35 m for patients with moderate to severe chronic obstructive pulmonary disease in order to represent an important effect. This corresponds to a 10% change of baseline 6-min walk distance. The low correlations of 6-min walk distance with patient-reported anchors question whether a minimal important difference exists for the 6-min walk distance.

MRI T2 lesion burden in multiple sclerosis: a plateauing relationship with clinical disability.

BACKGROUND: Previous studies have shown only modest correlation between multiple sclerosis (MS) lesions on MRI and clinical disability. OBJECTIVE: To investigate the relationship between proton density/T2-weighted (T2) burden of disease (BOD) quantitatively measured on MRI scans and clinical determinants including disability. METHODS: Using the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database, the authors studied baseline T2 BOD data from a pooled subsample of 1,312 placebo MS patients from 11 randomized controlled trials. Univariate comparisons guided development of multiple regression models incorporating the most important clinical predictors. RESULTS: Significant, although weak to moderate, correlations were found between T2 BOD and age at disease onset, disease duration, disease course, disability (as measured by the Expanded Disability Status Scale [EDSS]), relapse rate, certain presenting symptoms, and gadolinium enhancement. An unexpected but key finding that persisted in the multiple regression analyses was a plateauing relationship between T2 BOD and disability for EDSS values above 4.5. CONCLUSIONS: This study confirmed the limited correlation between clinical manifestations and T2 burden of disease (BOD) but revealed an important plateauing relationship between T2 BOD and disability.

Predictors of relapse rate in MS clinical trials.

BACKGROUND: The annual relapse rate has been commonly used as a primary efficacy endpoint in phase III multiple sclerosis (MS) clinical trials. The aim of this study was to determine the relative contribution of different possible prognostic factors available at baseline to the on-study relapse rate in MS. METHODS: A total of 821 patients from the placebo arms of the Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) database were available for this analysis. The univariate relationships between on-study relapse rate and the baseline demographic, clinical, and MRI-based predictors were assessed. The multiple relationships were then examined using a Poisson regression model. Two predictor subsets were selected. Subset 1 included age at disease onset, disease duration, sex, Expanded Disability Status Scale (EDSS) at baseline, number of relapses in the last 24 months prior to baseline, and the disease course (relapsing remitting [RR] and secondary progressive [SP]). Subset 2 consisted of Subset 1 plus gadolinium enhancement status in MRI. The number of patients for developing the models with no missing values was 727 for Subset 1 and 306 for Subset 2. RESULTS: The univariate relationships show that the on-study relapse rate was higher for younger and for female patients, for RR patients than for SP patients, and for patients with positive enhancement status at entry (Wilcoxon test, p < 0.05). A higher on-study relapse rate was associated with a shorter disease duration, lower entry EDSS, more pre-study relapses, and more enhancing lesions in T1 at entry. The fitted Poisson model shows that disease duration (estimate = -0.02) and previous relapse number (estimate = 0.59 for one, 0.91 for two, and 1.45 for three or more relapses vs no relapses) remain. The authors were able to confirm these findings in a second, independent dataset. CONCLUSIONS: The relapse number prior to entry into clinical trials together with disease duration are the best predictors for the on-study relapse rate. Disease course did not contribute independently because its effect is covered by the pre-study relapse rate. Gadolinium enhancement status, given the other covariates, has no significant influence on the on-study relapse rate.

Predicting gadolinium enhancement status in MS patients eligible for randomized clinical trials.

BACKGROUND: Gadolinium enhancement is often used in randomized clinical trials to evaluate the efficacy of new drugs in multiple sclerosis (MS). Knowledge about predictors of enhancement status is important for the selection of patients for MRI monitored trials. METHODS: Data from 17 trials were available in anonymized format through the Sylvia Lawry Centre for MS Research. In an open part containing 1,328 (non primary progressive) patients, two logistic regression analyses were explored, including demographic, clinical, and MRI predictors. The authors examined the area under the curve (AUC) and the increase in positive predictive value (PPV). The final selection of models was validated in a closed part of 848 comparable patients. RESULTS: Age at onset, disease duration, and disease course (CIS/RR/SP) were important predictors from the multivariate models. Further, a multivariate model including T2 burden of disease was more predictive than one with only clinical predictors (AUC 0.719 vs 0.625, p < 0.001). For the model with T2 burden of disease, the PPV was 66.8%, compared to 58.5% for the model without (a priori chance 46.4%). These findings were unequivocally confirmed in the closed part of the database. CONCLUSION: Gadolinium status can be predicted by a set of baseline variables, certainly when T2 burden of disease is included. These findings may benefit the design and statistical power of future randomized clinical trials.

Rec (formerly Corf) function requires interaction with a complex, folded RNA structure within its responsive element rather than binding to a discrete specific binding site.

It was recently reported that the human endogenous retrovirus HTDV/HERV-K encodes the regulatory protein Rec (formerly designated Corf), which is functionally equivalent to the nuclear export adapter proteins Rev of human immunodeficiency virus and Rex of human T-cell leukemia virus. We have demonstrated that the Rec protein interacts with a characteristic 429-nucleotide RNA element, the Rec-responsive element (RcRE), present in the 3' long terminal repeat of HTDV/HERV-K transcripts. In analogy to the Rev and Rex proteins, which have distinct RNA binding sites in their responsive elements, we have proposed that Rec may also have a defined binding site in the RcRE. In this report, we demonstrate that not every HTDV/HERV-K copy present in the human genome contains an active RcRE, and we characterize mutations that abrogate Rec function. In addition, we demonstrate that Rec function requires binding to a complex, folded RNA structure rather than binding to a discrete specific binding site, in contrast to Rev and Rex and their homologous responsive elements. We define four stem-loop structures in the RcRE that are essential for Rec function. Finally, we demonstrate that both Rev and Rex can mediate nuclear export through the RcRE but that their binding sites are different from each other and from that of Rec.

[Topographic mapping of retinal function with a scanning laser ophthalmoscope and multifocal electroretinography using short M-sequences]. / Topograficheskoe kartirovanie funktsii setchatki pri ispol'zovanii skaniruiushchego lazernogo oftal'moskopa i M-posledovatel'nostei dlia mul'tifokal'noi élektroretinografii.

A new method of multifocal electroretinography making use of scanning laser ophthalmoscope with a wavelength of 630 nm (SLO-m-ERG), evoking short spatial visual stimuli on the retina, is proposed. Algorithm of presenting the visual stimuli and analysis of distribution of local electroretinograms on the surface of the retina is based on short m-sequences. Mathematical cross correlation analysis shows a three-dimensional distribution of bioelectrical activity of the retina in the central visual field. In normal subjects the cone bioelectrical activity is the maximum in the macular area (corresponding to the density of cone distribution) and absent in the blind spot. The method detects the slightest pathological changes in the retina under control of the site of stimulation and ophthalmoscopic picture of the fundus oculi. The site of the pathological process correlates with the topography of changes in bioelectrical activity of the examined retinal area in diseases of the macular area and pigmented retinitis detectable by ophthalmoscopy.