Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity.

Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies (nNationMS = 946, nBIONAT = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-ß-treated patients. In carriers of MC1R:rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS.

Soft Phonon Mode Triggering Fast Ag Diffusion in Superionic Argyrodite Ag8 GeSe6.

The structural coexistence of dual rigid and mobile sublattices in superionic Argyrodites yields ultralow lattice thermal conductivity along with decent electrical and ionic conductivities and therefore attracts intense interest for batteries, fuel cells, and thermoelectric applications. However, a comprehensive understanding of their underlying lattice and diffusive dynamics in terms of the interplay between phonons and mobile ions is missing. Herein, inelastic neutron scattering is employed to unravel that phonon softening on heating to Tc ≈ 350 K triggers fast Ag diffusion in the canonical superionic Argyrodite Ag8 GeSe6 . Ab initio molecular dynamics simulations reproduce the experimental neutron scattering signals and identify the partially ultrafast Ag diffusion with a large diffusion coefficient of 10-4 cm-2 s-1 . The study illustrates the microscopic interconnection between soft phonons and mobile ions and provides a paradigm for an intertwined interaction of the lattice and diffusive dynamics in superionic materials.

Axillary Node Metastases of Medullary Thyroid Cancer: A Hallmark of Terminal Disease.

Little is known about axillary node metastasis of medullary thyroid cancer (MTC). To address this, a comparative study of patients with and without axillary node metastases of MTC was conducted. Among 1215 consecutive patients with MTC, 482 patients had node-negative MTC and 733 patients node-positive MTC. Among the 733 patients with node-positive MTC, 4 patients (0.5%) had axillary node metastases, all of which were ipsilateral. Patients with axillary node metastases had 5.7-6.9-fold more node metastases removed, both at the authors' institution (medians of 34.5 vs. 5 metastases; p=0.011) and in total (medians of 57 vs. 10 metastases; p=0.013), developed more frequently distant metastases (3 of 4 vs. 178 of 729 patients, or 75 vs. 24%; p=0.049), specifically to bone (2 of 4 vs. 67 of 729 patients, or 50 vs. 9%; p=0.046) and brain (1 of 4 vs. 4 of 729 patients, or 25 vs. 0.5%; p=0.027), and more often succumbed to cancer-specific death (3 of 4 vs. 52 of 729 patients, or 75 vs. 14%; p=0.005). Altogether, patients with axillary node metastases revealed 4-8-fold more node metastases in the ipsilateral lateral neck (medians of 11 vs. 3 metastases; p=0.021) and in the ipsilateral central neck (medians of 8 vs. 1 metastases; p=0.079) patients without axillary node metastases. Cancer-specific survival of patients with vs. patients without axillary node metastases of MTC was significantly shorter (means of 41 vs. 224 months; plog-rank<0.001). These findings show that patients with axillary node metastases of MTC have massive metastatic dissemination with poor survival.

Early spinal cord pseudoatrophy in interferon-beta-treated multiple sclerosis.

BACKGROUND AND PURPOSE: Brain pseudoatrophy has been shown to play a pivotal role in the interpretation of brain atrophy measures during the first year of disease-modifying therapy in multiple sclerosis. Whether pseudoatrophy also affects the spinal cord remains unclear. The aim of this study was to analyze the extent of pseudoatrophy in the upper spinal cord during the first 2 years after therapy initiation and compare this to the brain. METHODS: A total of 129 patients from a prospective longitudinal multicentric national cohort study for whom magnetic resonance imaging scans at baseline, 12 months, and 24 months were available were selected for brain and spinal cord volume quantification. Annual percentage brain volume and cord area change were calculated using SIENA (Structural Image Evaluation of Normalized Atrophy) and NeuroQLab, respectively. Linear mixed model analyses were performed to compare patients on interferon-beta therapy (n = 84) and untreated patients (n = 45). RESULTS: Patients treated with interferon-beta demonstrated accelerated annual percentage brain volume and cervical cord area change in the first year after treatment initiation, whereas atrophy rates stabilized to a similar and not significantly different level compared to untreated patients during the second year. CONCLUSIONS: These results suggest that pseudoatrophy occurs not only in the brain, but also in the spinal cord during the first year of interferon-beta treatment.

Improved Decision Making for Water Lead Testing in U.S. Child Care Facilities Using Machine-Learned Bayesian Networks.

Tap water lead testing programs in the U.S. need improved methods for identifying high-risk facilities to optimize limited resources. In this study, machine-learned Bayesian network (BN) models were used to predict building-wide water lead risk in over 4,000 child care facilities in North Carolina according to maximum and 90th percentile lead levels from water lead concentrations at 22,943 taps. The performance of the BN models was compared to common alternative risk factors, or heuristics, used to inform water lead testing programs among child care facilities including building age, water source, and Head Start program status. The BN models identified a range of variables associated with building-wide water lead, with facilities that serve low-income families, rely on groundwater, and have more taps exhibiting greater risk. Models predicting the probability of a single tap exceeding each target concentration performed better than models predicting facilities with clustered high-risk taps. The BN models' Fß-scores outperformed each of the alternative heuristics by 118-213%. This represents up to a 60% increase in the number of high-risk facilities that could be identified and up to a 49% decrease in the number of samples that would need to be collected by using BN model-informed sampling compared to using simple heuristics. Overall, this study demonstrates the value of machine-learning approaches for identifying high water lead risk that could improve lead testing programs nationwide.

A Prospective Randomized Controlled Pilot Study to Assess the Response and Tolerability of Cold Atmospheric Plasma for Rosacea.

INTRODUCTION: Rosacea is a common, facial, chronic inflammatory skin disease. Due to its complex pathogenesis, adequate therapy of rosacea can be challenging. An innovative recent therapeutic tool is cold atmospheric plasma (CAP), which is already established in the treatment of chronic wounds and promising in different other skin diseases. METHODS: In a split-face pilot study we investigated dielectric-barrier-discharged CAP in erythemato-telangiectatic (ETR) and/or papulopustular rosacea (PPR). CAP treatment was applied on lesional skin of a randomized side once daily (90 s/area) for 6 weeks. The other untreated side served as control. Co-primary endpoints were ≥1 improvement of the Investigator Global Assessment (IGA) score on the treated side compared to control and a decline of the Dermatology Life Quality Index (DLQI) after 6 weeks. Secondary endpoints included inflammatory lesion count (papules and pustules), skin redness intensity and erythema size. Adverse events (AEs) were recorded constantly. Additionally, participants were weekly assessed for symptoms, skin condition, trigger factors, skin care, treatment success, and local tolerance parameters. All p values were calculated using the Wilcoxon signed-rank test. RESULTS: Twelve subjects (ETR, n = 3; ETR and PPR, n = 9) completed the study. DLQI was significantly improved after 6 weeks (p = 0.007). On the CAP-treated side, lesions (p = 0.007) and erythema size (p = 0.041) were significantly reduced compared to the control. IGA (p = 0.2) and skin redness intensity (p = 0.5) did not differ significantly between control and CAP-treated side. No serious AEs occurred and treatment was well tolerated. CONCLUSION: CAP is a promising new treatment of rosacea, especially for PPR.

Performance and cost-benefit analysis of anaerobic moving bed biofilm reactor for pretreatment of textile wastewater.

Performance of an anaerobic moving bed biofilm reactor (AnMBBR) was evaluated for pretreatment of real textile desizing wastewater at organic loading rate (OLR) of 1±0.05 to 6.3±0.37 kgCOD/m3/d. After OLR optimization, the performance of AnMBBR was evaluated for biodegradation of reactive dyes. AnMBBR was operated under a mesophilic temperature range of 30 to 36 °C, while the oxidation-reduction potential (ORP) and pH were in the range of 504 to 594 (-mV) and 6.98 to 7.28, respectively. By increasing the OLR from 1±0.05 to 6.3±0.37 kgCOD/m3/d, COD and BOD5 removal was decreased from 84 to 39% and 89 to 49%, respectively. While the production of biogas was increased from 0.12 to 0.83 L/L·d up to an optimum OLR of 4.9±0.43 kgCOD/m3/d. With increase in the dye concentration in the feed, COD, BOD5, color removal and biogas production reduced from 56, 63, 70% and 0.65 L/L·d to 34, 43, 41% and 0.08 L/L·d, respectively. Based on the data obtained, a cost-benefit analysis of AnMBBR was also investigated for the pretreatment of real textile desizing wastewater. Cost estimation of anaerobic pretreatment of textile desizing wastewater indicated a net profit of 21.09 million PKR/yr (114,000 €/yr) and a potential payback period of 2.54 years.

Clonidine suppression test for a reliable diagnosis of pheochromocytoma: When to use.

OBJECTIVE: In clinical practice, false-positive results in biochemical testing for suspected pheochromocytoma/paraganglioma (PPGL) are not infrequent and may lead to unnecessary examinations. We aimed to evaluate the role of the clonidine suppression test (CST) in the era of analyses of plasma-free metanephrines for the diagnosis or exclusion of PPGL in patients with adrenal tumours and/or arterial hypertension. DESIGN AND METHODS: This single-centre, prospective trial investigated the use of CST in 60 patients with suspected PPGL associated with out-patient elevations of plasma normetanephrine (NMN) and/or metanephrine (MN), in most cases accompanied with hypertension or an adrenal mass. Measurements of plasma catecholamines and free metanephrines were performed by liquid chromatography with electrochemical detection and tandem mass spectrometry, respectively. RESULTS: Forty-six patients entered final analysis (n = 20 with PPGL and n = 26 with a nonfunctional adrenal mass and/or hypertension). CST reliably excluded false-positive baseline NMN results with a specificity of 100%. The sensitivity of CST improved from 85% to 94% when tumours with isolated MN increase (n = 3) were not considered. In patients with elevated baseline NMN (n = 24), CST correctly identified all patients without PPGL. Patients with falsely elevated baseline NMN results (n = 7, 26.9%) exhibited increases of baseline NMN up to 1.7-fold above the upper reference limit. CONCLUSION: CST qualifies as a useful diagnostic tool for differential diagnosis of borderline elevated plasma-free NMN in patients with suspected PPGL. In this context, CST helps to correctly identify all false-positive NMN screening results.

Risk Patterns of Distant Metastases in Follicular, Papillary and Medullary Thyroid Cancer.

This study of 542 patients with follicular thyroid cancer, 366 patients with the follicular variant and 1452 patients with the classical variant of papillary thyroid cancer, and 819 patients with sporadic medullary thyroid cancer operated at a tertiary referral center aimed to determine risk patterns of distant metastasis for each tumor entity, which are ill-defined. On multivariable logistic regression analyses, lymph node metastasis consistently emerged as an independent risk factor of distant metastasis, yielding odds ratios (ORs) of 2.4 and 2.8 for follicular thyroid cancer and the follicular variant of papillary thyroid cancer, and ORs of 5.9 and 6.4 for the classical variant of papillary thyroid cancer and sporadic medullary thyroid cancer. Another independent risk factor consistently associated with distant metastasis, most strongly in follicular thyroid cancer and the follicular variant of papillary thyroid cancer (OR 3.5 and 4.0), was patient age >60 years. Altogether, 2 distinct risk patterns of distant metastasis were identified, which were modulated by other cancer type-dependent risk factors: one with lymph node metastasis as leading component (classical variant of papillary thyroid cancer and sporadic medullary thyroid cancer), and another one with age as leading component (follicular thyroid cancer and the follicular variant of papillary thyroid cancer). Distant metastasis was exceptional in node-negative patients with sporadic medullary thyroid cancer (1.7%) and the classical variant of papillary thyroid cancer (1.4%), and infrequent in node-negative patients with the follicular variant of papillary thyroid cancer (4.4%). These findings delineate windows of opportunity for early surgical intervention before distant metastasis has occurred.

Lead Levels in Tap Water at Licensed North Carolina Child Care Facilities, 2020-2021.

Objectives. To evaluate lead levels in tap water at licensed North Carolina child care facilities. Methods. Between July 2020 and October 2021, we enrolled 4005 facilities in a grant-funded, participatory science testing program. We identified risk factors associated with elevated first-draw lead levels using multiple logistic regression analysis. Results. By sample (n = 22 943), 3% of tap water sources exceeded the 10 parts per billion (ppb) North Carolina hazard level, whereas 25% of tap water sources exceeded 1 ppb, the American Academy of Pediatrics' reference level. By facility, at least 1 tap water source exceeded 1 ppb and 10 ppb at 56% and 12% of facilities, respectively. Well water reliance was the largest risk factor, followed by participation in Head Start programs and building age. We observed large variability between tap water sources within the same facility. Conclusions. Tap water in child care facilities is a potential lead exposure source for children. Given variability among tap water sources, it is imperative to test every source used for drinking and cooking so appropriate action can be taken to protect children's health. (Am J Public Health. 2022;112(S7):S695-S705. https://doi.org/10.2105/AJPH.2022.307003).

Metastatic Risk Profile of Microscopic Lymphatic and Venous Invasion in Medullary Thyroid Cancer.

The metastatic risk profile of microscopic lymphatic and venous invasion in medullary thyroid cancer is ill-defined. This evidence gap calls for evaluation of the suitability of microscopic lymphatic and venous invasion at thyroidectomy for prediction of lymph node and distant metastases in medullary thyroid cancer. In this study of 484 patients with medullary thyroid cancer who had≥5 lymph nodes removed at initial thyroidectomy, microscopic lymphatic and venous invasion were significantly associated with greater primary tumor size (27.6 vs. 14.5 mm, and 30.8 vs. 16.2 mm) and more frequent lymph node metastasis (97.0 vs. 25.9%, and 85.2 vs. 39.5%) and distant metastasis (25.0 vs. 5.1%, and 32.8 vs. 7.3%). Prediction of lymph node metastases by microscopic lymphatic invasion was better than prediction of distant metastases by microscopic venous invasion regarding sensitivity (97.0 vs. 32.8%) and positive predictive value (58.4 vs. 39.2%); comparable regarding negative predictive value (98.5 vs. 90.5%) and accuracy (80.4 vs. 85.1%); and worse regarding specificity (74.1 vs. 92.7%). On multivariable logistic regression, microscopic lymphatic invasion predicted lymph node metastasis better (odds ratio [OR] 65.6) than primary tumor size (OR 4.6 for tumors>40 mm and OR 2.7 for tumors 21-40 mm, relative to tumors≤20 mm), whereas primary tumor size was better in predicting distant metastasis (OR 8.3 for tumors>40 mm and OR 3.9 for tumors 21-40 mm, relative to tumors≤20 mm) than microscopic venous invasion (OR 3.2). These data show that lymphatic invasion predicts lymph node metastases better in medullary thyroid cancer than venous invasion heralds distant metastases.

Distinct Late-Night Salivary Cortisol Cut-Off Values for the Diagnosis of Hypercortisolism.

Due to high morbidity and mortality of untreated hypercortisolism, a prompt diagnosis is essential. Measurement of late-night salivary cortisol provides a simple and non-invasive method. However, thresholds and reference ranges differ among studies. The goal of this study was to define a threshold of late-night salivary cortisol for the diagnosis of hypercortisolism based on the used assay. Moreover, the influence of different aetiologies of hypercortisolism and individual comorbidities were investigated. Prospective analyses of 217 patients, including 36 patients with proven hypercortisolism were carried out. A sum of 149 patients with suspicion of hypercortisolism but negative endocrine testing and 32 patients with hypercortisolism in remission served as control group. Late-night salivary cortisol was measured using an automated chemiluminescence immunoassay. Cut-off values were calculated by ROC analysis. The calculated cut-off value for the diagnosis of hypercortisolism was 10.1 nmol/l (sensitivity 94%; specificity 84%). Only slightly lower thresholds were obtained in patients with suspected hypercortisolism due to weight gain/obesity (9.1 nmol/l), hypertension or adrenal tumours (both 9.8 nmol/l) or pituitary adenomas (9.5 nmol/l). The late-night salivary cortisol threshold to distinguish between Cushing's disease and Cushing's disease in remission was 9.2 nmol/l. The cut-off value for the diagnosis of ectopic ACTH-production was 109.0 nmol/l (sensitivity 50%, specificity 92%). Late-night salivary cortisol is a convenient and reliable parameter for the diagnosis of hypercortisolism. Except for ectopic ACTH-production, thresholds considering different indications for evaluation of hypercortisolism were only slightly different. Therefore, they might only be useful if late-night salivary cortisol results near the established cut-off value are present.

Analysis of risk factors and prognosis in differentiated thyroid cancer with focus on minimal extrathyroidal extension.

AIMS: In contrast to all prior AJCC/TNM classifications for differentiated thyroid cancer (DTC) the 8th edition does not take minimal extrathyroidal extension (M-ETE) into consideration for local tumor staging. We therefore aimed to retrospectively assess the specific impact of M-ETE on the outcome of M-ETE patients treated in our clinic. METHODS: DTC patients with M-ETE and a follow-up time of ≥ 5 years were included and matched with an identical number of patients without M-ETE, but with equal histopathological tumor subtype and size. The frequency of initially metastatic disease among groups was compared using Fisher's exact test, the recurrence rate by virtue of log-rank test. Fisher's exact test and multivariate analysis were used to account for the presence of confounding risk factors. RESULTS: One hundred sixty patients (80 matching pairs) were eligible. With other confounding risk factors being equal, the prevalence of N1-/M1-disease at initial diagnosis was comparable among groups (M-ETE: 42.5 %; no M-ETE: 32.5 %; p = 0.25). No differences with regard to the recurrence rate were shown. However, M-ETE patients were treated with external beam radiation therapy more often (16.3 % vs. 1.3 %; p = 0.004) and received higher median cumulative activities of 131I (10.0 vs. 8.0 GBq; p < 0.001). DISCUSSION: Although having played a pivotal role for local tumor staging of DTC for decades M-ETE did not increase the risk for metastases at initial diagnosis and the recurrence rate in our cohort. Patients with M-ETE had undergone intensified treatment, which entails a possible confounding factor that warrants further investigation in randomized controlled trials.

Midlatency auditory evoked potentials during anesthesia in children: A narrative review.

The brain is considered as the major target organ of anesthetic agents. Despite that, a reliable means to monitor its function during anesthesia is lacking. Mid latency auditory evoked potentials are known to be sensitive to anesthetic agents and might therefore be a measure of hypnotic state in pediatric patients. This review investigates the available literature describing various aspects of mid latency auditory evoked potential monitoring in pediatric anesthesia.

The performance of the heart rate variability-derived Newborn Infant Parasympathetic Evaluation Index as a measure of early postoperative pain and discomfort in infants-A prospective observational study.

BACKGROUND: The heart rate variability-derived Newborn Infant Parasympathetic Evaluation (NIPE™) Index is a continuous noninvasive tool for the assessment of pain and discomfort in infants. Little is known about its performance in the early postoperative setting, where assessment of pain/discomfort is usually based on discontinuous observational scoring systems or personal experience of medical staff. AIMS: To investigate the performance of the NIPE as a measure of early postoperative pain and/or discomfort in infants. METHODS: The potential of the NIPE to detect pain/discomfort, as assessed by two clinical scoring systems (FLACC and COMFORT-B scale), was investigated in postoperative infants (0-2 years). RESULTS: Receiver operating curve (ROC) analyses investigating the power of the NIPE to distinguish between comfort and pain/discomfort, revealed areas under the curve (AUC) of 0.77 for the FLACC, 0.81 for the COMFORT-B score, and 0.77 for a combination of FLACC & COMFORT-B. Logistic regression analysis provided initial evidence that the NIPE is an independent predictor of a FLACC score ≥4 and/or a COMFORT-B score ≥17, though R2 values were below .2. NIPE values associated with a FLACC ≥4 (48 [45-56]), a COMFORT-B score ≥17 (47 [42-53]), and a FLACC ≥4 & COMFORT-B ≥17 (47 [42-57]) were lower than NIPE values associated with a FLACC <4 (60 [53-68], 95% CI of difference -14 to -8, p < .0001), a COMFORT-B score <17 (61 [54-68], 95% CI of difference -16 to -10, p < .0001), and a FLACC <4 & COMFORT-B score <17 (60 [53-68], 95% CI of difference -15 to -8, p < .0001). We found no evidence of a predictive value of the NIPE regarding the occurrence of pain. CONCLUSIONS: The NIPE detected pain and discomfort in infants after general anesthesia with reasonable areas under the ROC curve (±0.8), whereas it was not predictive of clinically detectable pain or discomfort.

The Response and Tolerability of a Novel Cold Atmospheric Plasma Wound Dressing for the Healing of Split Skin Graft Donor Sites: A Controlled Pilot Study.

INTRODUCTION: Cold atmospheric plasma (CAP) has positive effects on wound healing and antimicrobial properties. However, an ongoing challenge is the development of specific modes of application for different clinical indications. OBJECTIVES: We investigated in a prospective pilot study the response and tolerability of a newly developed CAP wound dressing for the acute healing of split skin graft donor sites compared to conventional therapy. METHODS: We applied both treatments to each patient (n = 10) for 7 days and measured 4 parameters of wound healing every other day (i.e., 1,440 measurements) using a hyperspectral imaging camera. Additionally, we evaluated the clinical appearance and pain levels reported by the patients. RESULTS: The CAP wound dressing was superior to the control (p < 0.001) in the improvement of 3 wound parameters, that is, deep tissue oxygen saturation, hemoglobin distribution, and tissue water distribution. CAP was well tolerated, and pain levels were lower in CAP-treated wound areas. CONCLUSION: CAP wound dressing is a promising new tool for acute wound healing.

[Multiple sclerosis treatment consensus group (MSTCG): position paper on disease-modifying treatment of multiple sclerosis 2021 (white paper)]. / Multiple Sklerose Therapie Konsensus Gruppe (MSTKG): Positionspapier zur verlaufsmodifizierenden Therapie der Multiplen Sklerose 2021 (White Paper).

Multiple sclerosis is a complex, autoimmune-mediated disease of the central nervous system characterized by inflammatory demyelination and axonal/neuronal damage. The approval of various disease-modifying therapies and our increased understanding of disease mechanisms and evolution in recent years have significantly changed the prognosis and course of the disease. This update of the Multiple Sclerosis Therapy Consensus Group treatment recommendation focuses on the most important recommendations for disease-modifying therapies of multiple sclerosis in 2021. Our recommendations are based on current scientific evidence and apply to those medications approved in wide parts of Europe, particularly German-speaking countries (Germany, Austria, Switzerland).

Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis.

OBJECTIVE: To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). METHODS: Serum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with early MS with stringent inclusion criteria. Epstein-Barr nuclear antigen (EBNA)-1 and viral capsid antigen (VCA) antibodies were measured in diluted sera by chemiluminescence immunoassays (CLIAs). Sera of EBNA-1 and VCA antibody-negative patients were retested undiluted by an EBV IgG immunoblot. For comparison, we retrospectively analysed the EBV seroprevalence across different age cohorts, ranging from 0 to >80 years, in a large hospital population (N=16 163) from Berlin/Northern Germany. RESULTS: EBNA-1 antibodies were detected by CLIA in 839 of 901 patients with CIS/RRMS. Of the 62 patients without EBNA-1 antibodies, 45 had antibodies to VCA as detected by CLIA. In all of the remaining 17 patients, antibodies to EBV were detected by immunoblot. Altogether, 901 of 901 (100%) patients with CIS/RRMS were EBV-seropositive. EBV seropositivity increased with age in the hospital population but did not reach 100% in any of the investigated age cohorts. CONCLUSION: The complete EBV seropositivity in this large cohort of patients with early MS strengthens the evidence for a role of EBV in MS. It also suggests that a negative EBV serology in patients with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS.

Monitoring Depth of Hypnosis: Mid-Latency Auditory Evoked Potentials Derived aepEX in Children Receiving Desflurane-Remifentanil Anesthesia.

BACKGROUND: The aepEXplus monitoring system, which uses mid-latency auditory evoked potentials to measure depth of hypnosis, was evaluated in pediatric patients receiving desflurane-remifentanil anesthesia. METHODS: Seventy-five patients, 1-18 years of age (stratified for age; 1-3, 3-6, 6-18 years, for subgroup analyses), were included in this prospective observational study. The aepEX and the bispectral index (BIS) were recorded simultaneously, the latter serving as a reference. The ability of the aepEX to detect different levels of consciousness, defined according to the University of Michigan Sedation Scale, investigated using prediction probability (Pk), and receiver operating characteristic (ROC) analysis, served as the primary outcome parameter. As a secondary outcome parameter, the relationship between end-tidal desflurane and the aepEX and BIS values were calculated by fitting in a nonlinear regression model. RESULTS: The Pk values for the aepEX and the BIS were, respectively, .68 (95% CI, 0.53-0.82) and .85 (95% CI, 0.73-0.96; P = .02). The aepEX and the BIS had an area under the ROC curve of, respectively, 0.89 (95% CI, 0.80-0.95) and 0.76 (95% CI, 0.68-0.84; P = .04). The maximized sensitivity and specificity were, respectively, 81% (95% CI, 61%-93%) and 86% (95% CI, 74%-94%) for the aepEX at a cutoff value of >52, and 69% (95% CI, 56%-81%) and 70% (95% CI, 57%-81%) for the BIS at a cutoff value of >65. The age-corrected end-tidal desflurane concentration associated with an index value of 50 (EC50) was 0.59 minimum alveolar concentration (interquartile range: 0.38-0.85) and 0.58 minimum alveolar concentration (interquartile range: 0.41-0.70) for, respectively, the aepEX and BIS (P = .69). Age-group analysis showed no evidence of a difference regarding the area under the ROC curve or EC50. CONCLUSIONS: The aepEX can reliably differentiate between a conscious and an unconscious state in pediatric patients receiving desflurane-remifentanil anesthesia.

Long-term outcome of surgical resection in patients with gastroenteropancreatic neuroendocrine neoplasia: results from a German nation-wide multi-centric registry.

BACKGROUND: Neuroendocrine neoplasia (NEN) are rare and heterogenous tumours. Few data exist on the impact of surgical therapy. MATERIALS AND METHODS: This is a retrospective analysis of prospectively collected data of gastroenteropancreatic NEN in the German NET-Registry (1999-2012). It focuses on patients without distant metastases (limited disease, LD, stage I-IIIB). RESULTS: Data of 2239 patients with NEN were recorded. Median age was 59 years, the gender ratio was 1:1.3 (f:m). A total of 986 patients (44%) had LD, and the 5-year survival rate (5 years) was 77% for all and 90% for patients with LD. A total of 1635 patients (73%) received a surgical therapy (1st to 6th line); the 5 and 10 ysr were 83/65% after and 59/35% without surgery for all patients (p < .001). The resection margins in the LD patients were 76%, 16%, and 3% for R0, R1 and R2, respectively. The 10 ysr was 84%, 59% and 42% for R0, R1 and R2 resections, respectively (p = .021 R0/R1, p < .001 R0/R2). The R0 resection rate was 75% for G1/G2 NET and 67% for G3 NEC. CONCLUSION: The rate of complete tumour resection (R0) in LD is independent of tumour grading, and R0 resection is the key determinant of long-term survival, as demonstrated by the 10 ysr. of 84%. All NEN patients with limited disease should be considered for operation, if possible, as the best 10-year survival is shown after an R0 resection.