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BACKGROUND To improve the sensitivity of the EEG in the diagnosis and classification of seizures or epilepsy, long-term recording with inferior temporal electrodes are recommended. MATERIAL AND METHODS The spatial distribution of epileptiform discharges from 24‑h EEG with 25 electrodes (10-20, extended by F9/F10, T9/T10, P9/P10) was retrospectively analyzed in 25 cases. RESULTS Maximum negativity was located below the 10-20 electrodes in 84%. Epileptiform discharges were more clearly detected on inferior temporal electrodes in 64%. In the intention-to-test population of 77 patients the number needed to test with extra electrodes was estimated as 5. CONCLUSION Recording EEG with 25 electrodes for 24 h improves the detection and localization of temporal epileptiform discharges also in geriatric patients with suspected nonlesional epilepsy.

We characterized the profile of Crohn’s disease (CD) or ulcerative colitis (UC) biologic-naive patients (starting a new therapy with vedolizumab or TNFα-antagonists), their baseline disease activity predictors, and their perception of the quality of life (HRQoL). The VEDOIBD-Study is a real-world study on the effectiveness of vedolizumab vs other biologics as induction and maintenance therapy for CD and UC. A total of 627 CD and 546 UC patients were enrolled from IBD-experienced centers across Germany. In both biologic-naive vedolizumab (n=397) and anti-TNF (n=359) patients, CD and UC disease severity and HRQoL predictors were analyzed with logistic regression. The results were reported as odds ratio (OR) and 95% confidence interval (CI). When compared to biologic-naive anti-TNF patients, a first biological therapy with vedolizumab was considered for older CD patients, with a less complicated though longer disease course, and with a history of comorbidities. No differences in (unmet) needs were observed among patients with UC. The presence of extra-intestinal manifestations in biologic-naive anti-TNF patients with CD (OR (95% CI): 3.83 (1.69–8.68)) and, in both biologic-naive groups of patients with UC, stool frequency (2.00 (1.25–3.19); 1.82 (1.10–3.02), respectively) and rectal bleeding (2.24 (1.20–4.18); 1.92 (1.19–3.11), respectively) emerged as the most important predictors of disease severity, which in turn were also significantly associated with a worse HRQoL. This study highlights the existence of unmet medical needs of patients with CD or UC, for whom a new biological therapy is planned as part of the VEDOIBD-Study, which considerably impacts their HRQoL.

ZusammenfassungDiese Handlungsempfehlung soll eine Grundlage für die Qualitätssicherung der Radiosynoviorthese (RSO) bei entzündlichen (nichtinfektiösen) Gelenkerkrankungen schaffen. Sie wurde interdisziplinär erarbeitet und beschreibt die allgemeine Zielsetzung, Definitionen, klinische Hintergrundinformationen und Kontraindikationen dieser Radionuklidtherapie. Aufgeführt werden die Anforderungen, die an ein Behandlungszentrum gestellt werden, prätherapeutisch notwendige Untersuchungsbefunde sowie Empfehlungen, wie die Behandlung technisch und organisatorisch durchgeführt werden sollte. Ferner finden sich Angaben zur Kontrolle und Nachsorge der therapierten Patienten. Grundsätzlich sollen Behandlung und Nachsorge in Abstimmung und Zusammenarbeit der beteiligten Fachdisziplinen erfolgen.

Aphasie ist ein typisches Symptom links fronto-temporaler Lasionen. Nicht selten werden aphasische Symptome jedoch auch nach subkortikalen Lasionen z. B. im Thalamus beschrieben. Als Ursache fur aphasische Symptome bei Thalamusschadigungen vermutet man die Storung eines thalamo-kortikalen Sprachnetzwerkes. Die Rolle des Thalamus in Sprachfunktionen wird in einer Rekrutierung sprachrelevanter, kortikaler Areale im Sinne einer Monitorfunktion vermutet. Wir berichten uber einen 72-jahrigen Patienten, der nach einem isolierten, links-anterioren Thalamusinfarkt eine expressiv betonte Aphasie gezeigt hat, und geben einen Uberblick zu pathophysiologischen Konzepten. Aphasia is a language disturbance typically associated with left fronto-temporal lesions. However, aphasic symptoms can also be seen after subcortical lesions, for example in the thalamus. Thalamic aphasia is thought to occur after disruption of a thalamo-cortical language networks. The thalamus is considered to act as a monitor, engaging specific cortical areas need for language functions. We report on a 72-year old male patient who presented with aphasia following a left-anterior ischemic stroke of the thalamus and present a review of the relevant literature.

International audience; BACKGROUND: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. METHODS: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0-1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0-2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4-6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. FINDINGS: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10-2·03]; p=0·011), with low heterogeneity across studies (I(2)=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05-1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06-2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4-6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52-1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03-4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [\textless1%], adjusted OR 5·58 [1·22-25·50]; p=0·024). INTERPRETATION: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. FUNDING: None.

Pubertierende Jugendliche sind eine Zielgruppe, die man erst einmal erreichen muss. Dabei ist es besonders wichtig, gerade Heranwachsende fur Vorsorgen zu gewinnen. Jugendarzte haben hier die Moglichkeit, durch Fruherkennung von Risikofaktoren einer Fehlentwicklung in der Pubertat entgegenzuwirken.

Aphasic symptoms are typically associated with lesions of the left fronto-temporal cortex. Interestingly, aphasic symptoms have also been described in patients with thalamic strokes in anterior, paramedian or posterolateral location. So far, systematic analyses are missing. We conducted a retrospective analysis of consecutive patients admitted to our tertiary stroke care center between January 2016 and July 2017 with image-based (MRI) proven ischemic stroke. We evaluated stroke lesion location, using 3-T MRI, and presence of aphasic symptoms. Out of 1064 patients, 104 (9.8%) presented with a thalamic stroke, 52 of which (4.9%) had an isolated lesion in the thalamus (ILT). In patients with ILT, 6/52 had aphasic symptoms. Aphasic symptoms after ILT were only present in patients with left anterior lesion location (n = 6, 100% left anterior vs. 0% other thalamic location, p

Background and Purpose— Many patients with acute ischemic stroke are not eligible for thrombolysis or mechanical reperfusion therapies due to contraindications, inaccessible vascular occlusions, late presentation, or large infarct core. Sphenopalatine ganglion (SPG) stimulation to enhance collateral flow and stabilize the blood-brain barrier offers an alternative, potentially more widely deliverable, therapy. Methods— In a randomized, sham-controlled, double-masked trial at 41 centers in 7 countries, patients with anterior circulation ischemic stroke not treated with reperfusion therapies within 24 hours of onset were randomly allocated to active SPG stimulation or sham control. The primary efficacy outcome was improvement beyond expectations on the modified Rankin Scale of global disability at 90 days (sliding dichotomy), assessed in the modified intention-to-treat population. The initial planned sample size was 660 patients, but the trial was stopped early when technical improvements in device placement occurred, so that analysis of accumulated experience could be conducted to inform a successor trial. Results— Among 303 enrolled patients, 253 received at least one active SPG or sham stimulation, constituting the modified intention-to-treat population (153 SPG stimulation and 100 sham control). Age was median 73 years (interquartile range, 64–79), 52.6% were female, deficit severity on the National Institutes of Health Stroke Scale was median 11 (interquartile range, 9–15), and time from last known well median 18.6 hours (interquartile range, 14.5–22.5). For the primary outcome, improved 3-month disability beyond expectations, rates in the SPG versus sham treatment groups were 49.7% versus 40.0%; odds ratio, 1.48 (95% CI, 0.89–2.47); P =0.13. A significant treatment interaction with stroke location (cortical versus noncortical) was noted, P =0.04. In the 87 patients with confirmed cortical involvement, rates of improvement beyond expectations were 50.0% versus 27.0%; odds ratio, 2.70 (95% CI, 1.08–6.73); P =0.03. Similar response patterns were observed for all prespecified secondary efficacy outcomes. No differences in mortality or serious adverse event safety end points were observed. Conclusions— SPG stimulation within 24 hours of onset is safe in acute ischemic stroke. SPG stimulation was not shown to statistically significantly improve 3-month disability above expectations, though favorable outcomes were nominally higher with SPG stimulation. Beneficial effects may distinctively be conferred in patients with confirmed cortical involvement. The results of this study need to be confirmed in a larger pivotal study. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03767192.

Background: Elevated high-sensitive cardiac troponin (hs-cTn) can be found in more than 50% of the patients with acute ischemic stroke. The observational TRoponin ELevation in Acute ischemic Stroke (TRELAS) study revealed that about 25% of all stroke patients with elevated troponin had a coronary angiography-detected culprit lesion affording immediate intervention, and about 50% of all patients did not have any obstructive coronary artery disease. Given the risk of procedure-related complications, the identification of stroke patients in urgent need of invasive coronary angiography is desirable. Methods: TRELAS patients were prospectively enrolled into this sub-study. In addition to conventional coronary angiography, a cardiac magnetic resonance imaging (MRI) at 3T was performed during the in-hospital stay after acute ischemic stroke to compare the diagnostic value of both imaging modalities. Results:Nine stroke patients (median age 73 years [range 58–87]; four females; median NIH Stroke Severity score on admission 4 [range 0–6] with elevated hs-cTnT [median 74 ng/L, interquartile range 41–247] on admission) completed cardiac MRI and underwent coronary angiography. The absence of MRI-detected wall motion abnormalities and/or late gadolinium enhancement in 5 stroke patients corresponded with the exclusion of culprit lesions or significant coronary artery disease by coronary angiography. Four patients had abnormal MRI findings, whereof 2 showed evidence of myocardial infarction and in whom coronary angiography demonstrated a >70% stenosis of a coronary artery. Conclusions: The TRELAS sub-study indicates that noninvasive cardiac MRI may provide helpful information to identify stroke patients with or without acute coronary syndrome. Our findings might help to select stroke patients in urgent need of coronary angiography.

Background and aims This study examined differences in personality, psychological distress, and stress coping in inflammatory bowel disease (IBD) depending on type of disease and disease activity. We compared patients suffering from Crohn’s disease (CD) and ulcerative colitis (UC) with controls. While the literature is replete with distinctive features of the pathogenesis of IBD, the specific differences in psychological impairments are not well studied. Methods In this German national multicenter study, participants were recruited from 32 centers. Two hundred ninety-seven questionnaires were included, delivering vast information on disease status and psychological well-being based on validated instruments with a total of 285 variables. Results CD patients were more affected by psychological impairments than patients suffering from UC or controls. Importantly, patients with active CD scored higher in neuroticism (p Conclusions We identified specific aspects of psychological impairment in IBD depending on disease and disease activity. Our results underscore the need for psychological support and treatment particularly in active CD.

The shape of nanomaterials affects their colloidal properties, cellular uptake, and fate in the environment. The microbial origin and microenvironment can play a role in altering the shape of the nanomaterial. However, such studies have never been conducted. Here, we demonstrate that the selenium nanomaterials produced by Escherichia coli K-12 are stable and remain as BioSe-Nanospheres under thermophilic conditions, while those produced by anaerobic granular sludge transform to BioSe-Nanorods, due to a lower quantity of proteins coating these nanoparticles, which has been verified by proteomics analysis as well as using chemically synthesized selenium nanomaterials. Furthermore, the presence of Bacillus safensis JG-B5T transform the purified BioSe-Nanospheres produced by E. coli K-12 to BioSe-Nanorods, though they are not transformed in the absence of B. safensis JG-B5T. This is due to the production of peptidases by B. safensis JG-B5T that cleaves the protein coating the BioSe-Nanospheres produced by E. coli K-12, leading to their transformation to trigonal BioSe-Nanorods, which is the thermodynamically more stable state. These findings suggest that the fate of selenium and probably other redox-active elements released from the biological wastewater treatment units needs to be reevaluated and improved by including microbial criteria for better accuracy.

Zusammenfassung Einleitung Der Einfluss einer SARS-CoV-2-Infektion auf chronisch entzündliche Darmerkrankungen (CED) ist bislang nicht gut charakterisiert, und es ist unklar, ob diese eine Anpassung der immunsuppressiven Therapie erfordert. Methodik Für die retrospektive Dokumentation klinischer Parameter und Veränderungen einer immunsuppressiven Therapie von mit SARS-CoV-2 infizierten CED-Patienten wurde ein nationales Melderegister etabliert. Ergebnisse Insgesamt wurden nur 3 von 185 CED-Patienten (1,6 %) wegen abdomineller Symptome auf eine SARS-CoV-2-Infektion getestet. Im COVID-19-Krankheitsverlauf entwickelten 43,5 % Durchfall, abdominelle Schmerzen oder Hämatochezie (Hospitalisierungsrisiko mit vs. ohne abdominelle Symptome: 20,0 % vs. 10,6 %, p Diskussion Bei mit SARS-CoV-2 infizierten CED-Patienten traten häufig neue abdominelle Symptome bei Infektion auf. Diese führten aber nur selten zur SARS-CoV-2-Testung. Eine hohe CED-Aktivität zum Zeitpunkt des SARS-CoV-2-Nachweises war mit einem erhöhten Hospitalisierungsrisiko assoziiert.

Purpose Image texture is increasingly used to discriminate tissues and lesions in PET/CT. For quantification or in computer-aided diagnosis, textural feature analysis must produce robust and comparable values. Because statistical feature values depend on image count statistics, we investigated in depth the stability of Haralick features values as functions of acquisition duration, and for common image resolutions and reconstructions. Methods A homogeneous cylindrical phantom containing 9.6 kBq/ml Ge-68 was repeatedly imaged on a Siemens Biograph mCT, with acquisition durations ranging from three seconds to three hours. Images with 1.5, 2, and 4 mm isometrically spaced voxels were reconstructed with filtered back-projection (FBP), ordered subset expectation maximization (OSEM), and the Siemens TrueX algorithm. We analysed Haralick features derived from differently quantized (3 to 8-bit) grey level co-occurrence matrices (GLCMs) as functions of exposure E, which we defined as the product of activity concentration in a volume of interest (VOI) and acquisition duration. The VOI was a 50 mm wide cube at the centre of the phantom. Feature stability was defined for df/dE → 0. Results The most stable feature values occurred in low resolution FBPs, whereas some feature values from 1.5 mm TrueX reconstructions ranged over two orders of magnitude. Within the same reconstructions, most feature value-exposure curves reached stable plateaus at similar exposures, regardless of GLCM quantization. With 8-bit GLCM, median time to stability was 16 s and 22 s for FBPs, 18 s and 125 s for OSEM, and 23 s, 45 s, and 76 s for PSF reconstructions, with longer durations for higher resolutions. Stable exposures coincided in OSEM and TrueX reconstructions with image noise distributions converging to a Gaussian. In FBP, the occurrence of stable values coincided the disappearance of negatives image values in the VOI. Conclusions Haralick feature values depend strongly on exposure, but invariance exists within defined domains of exposure. Here, we present an easily replicable procedure to identify said stable exposure domains, where image noise does not substantially add to textural feature values. Only by imaging at predetermined feature-invariant exposure levels and by adjusting exposure to expected activity concentrations, can textural features have a quantitative use in PET/CT. The necessary exposure levels are attainable by modern PET/CT systems in clinical routine.

Women with inflammatory bowel diseases (IBD) often receive biologicals during pregnancy to maintain disease remission. Data on outcome of vedolizumab-exposed pregnancies (VDZE) are sparse., info:eu-repo/semantics/published

In his treatise “The Laws and Customs of Scotland in Matters Criminal”, which was first published in 1678, Sir George Mackenzie gave the first thorough account of Scots criminal law. Being heavily influenced by Roman and Civil Law authorities most of the latter ones hail from Italy, France, the Low Countries, and Spain. There are, however, also a number of German civilian authors Mackenzie relies on. Their influence on his line of argumentation is the subject of Thomas Krause's article.

Background The most common complication after ileal pouch anal anastomosis in up to 50% of patients is an acute pouchitis. The majority of patients respond to antibiotic treatment. However, 10%-15% develops chronic antibiotic-dependent or refractory pouchitis which is usually hard to treat. Aim To evaluate the effectiveness of vedolizumab in patients with chronic pouchitis. Methods Patients with chronic antibiotic-dependent or refractory pouchitis were treated with vedolizumab (300 mg at week 0, 2, 6 and 10) in 10 IBD centres and retrospectively registered. Data were recorded until week 14 of vedolizumab treatment. In total 20 patients (12 male, median age 43 years) were included for analysis. The effectiveness was measured using the Oresland Score (OS) at week 2, 6, 10 and 14 and the pouch disease activity index (PDAI) at week 0 and 14. Results The mean OS declined from 6.8 (range 2-12) to 3.4 (range 0-11). Concordantly, the mean PDAI after 14 weeks of treatment dropped from 10 (range 5-18) to 3 (range 0-10). Only three patients reported moderate side effects. No serious side effects were recorded. In addition, symptomatic co-medication such as loperamide and tincture of opium could be terminated in 8 out of 12 patients as well as antibiotic treatment could be stopped in 17 out of 19 patients. Conclusion Our data indicate that vedolizumab could be an option in the treatment of patients with chronic, antibiotic-dependent or refractory pouchitis.

Background Prospective, observational real world studies on the effectiveness and safety of ustekinumab (UST) in Crohn’s disease (CD) are required in addition to RCTs, usually confined to selected patients, which may not represent special treatment patterns and everyday clinical practice. The aim of the present 3-year RUN-CD study was to investigate the induction phase effectiveness of UST vs. other biologics (OB) in CD in terms of clinical and steroid-free remission at week 16. To the best of our knowledge, RUN-CD is currently the largest prospective real world evidence (RWE) study with UST in CD using propensity score adjustment. Methods Between 2017–2020, 901 CD-patients starting a new therapy with UST or OB, were enrolled in 44 IBD-experienced centers across Germany. After exclusion of missing outcomes, the final sample consisted of 657 patients. Clinical remission (HBI ≤ 4), and steroid-free remission (HBI ≤ 4 and no systemic use of steroids or budesonide during the last 8 weeks) were considered as outcomes at week 16. To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 339 UST (naïve: 34) and 318 OB CD-patients were included (ADA: 50.3%, IFX: 37.4%, VDZ: 12.3%) (naïve: 203). PS removed systematic differences between both groups (30.8% smokers, 15.1% perianal disease, 36.2% surgical resection, 40.5% EIM). The effectiveness of UST for clinical and steroid-free remission was comparable to that of OB at week 16. Besides, in bio-naïve patients, clinical remission was numerically, though not significantly, higher in UST vs OB (Table 1). Similar results were observed in the bio-experienced UST vs. OB groups [remission: 59.3% vs 55.4%; OR: 1.17 (0.73–1.90)]. For both the remission rates were higher in the bio-naïve than in the bio-experienced groups (p Conclusion In this prospective RUN-CD study, with propensity score weighted groups, UST showed similar induction effectiveness in comparison with OB therapies. Remarkably higher remission rates were observed in this RWE study than in prior RCTs. An additional favorable safety profile supports consideration of UST as a first-line targeted therapy for CD.

Purpose Avoiding measurement variability from 18F phantom preparation by using 68Ge/68Ga phantoms for the determination of 18F recovery curves (RC) in clinical quality assurance measurements and for PET/CT site qualification in multicentre clinical trials. Methods RCs were obtained from PET/CT measurements of seven differently sized phantom spheres filled either with 18F or with 68Ga. RCs for the respective other isotope were then determined by two different methods: In the first method, images were convolved with positron range transconvolution functions derived from positron annihilation distributions found in literature. This method generated re-casted images matching images using the respective other isotope. In the second method, the PET/CT system's isotope independent (intrinsic) point spread function was determined from said phantom measurements and convolved with numerical representations simulating hot spheres filled with the respective other isotope. These simulations included the isotope specific positron annihilation distributions. Recovered activity concentrations were compared between re-casted images, simulated images and the originally acquired images. Results 18F and 68Ga recovery was successfully determined from image acquisitions of the respective opposite isotope as well as from the simulations. 68Ga RCs derived from 18F data had a normalized root-mean-square deviation (NRMSD) from real 68Ga measurements of 0.019 % when using the first method and of 0.008 % when using the second method. 18F RCs derived from 68Ga data had a NRMSD from real 18F measurements of 0.036 % when using the first method and of 0.038 % when using the second method. Conclusions Applying the principles of transconvolution, 18F RCs can be recalculated from 68Ga phantom measurements with excellent accuracy. The maximal additionally introduced error was below 0.4% of the error currently accepted for RCs in the site qualification of multicentre clinical trials by the EARL program of the European Association of Nuclear Medicine (EANM). Therefore, our methods legitimately allow for the use of long-lived solid state 68Ge/68Ga phantoms instead of manually prepared 18F phantoms to characterize comparability of 18F measurements across different imaging sites or of longitudinal18F measurements at a single PET/CT system. This article is protected by copyright. All rights reserved.

Objective Elevated levels of cardiac troponin, and especially their relative changes over time, indicate acute myocardial injury. They are also frequently observed after acute ischemic stroke (AIS), indicating poor functional outcome and increased mortality. However, recent evidence showed that, in most AIS patients, myocardial injury is not caused by coronary ischemia. Instead, stroke lesion location has been suggested to precipitate myocardial injury. Methods Voxel-based lesion-symptom mapping (VLSM) was used in 299 patients who had a magnetic resonance imaging–confirmed acute ischemic stroke within the anterior circulation and a high-sensitivity cardiac troponin T (hs-cTnT) acquired on the day of admission. Of these, 228 had a second troponin measurement during the acute phase. The absolute hs-cTnT levels above the 99th percentile of a healthy reference population (≥14ng/l) as well as their relative temporal changes were used as continuous variables of interest in the VLSM model, including a multiple regression analysis adjusted for confounding variables. Results The anterior insular cortex of the right hemisphere, in particular its dorsal subregion, was significantly associated with the relative temporal changes of hs-cTnT (p

Morbid obesity in both adolescents and adults has risen in an alarming rate. Bariatric surgery is playing an increasing role in pediatric surgery. However, current evidence is limited regarding its safety and outcome.Since 2005, data from obese patients that undergo bariatric procedures in Germany are prospectively registered. For the current analysis, all adolescent and adult subjects that had undergone laparoscopic sleeve gastrectomy (LSG) from 2005 to 2014 were considered.LSG represents the most common bariatric procedure in Germany with a proportion of 48.1% in adolescent and 48.7% in adult obese in 2014. LSG was performed in 362 adolescent and 15,428 adult subjects. Pre-operative BMI was comparable between the two populations. However, adult obese had more frequently coexisting comorbidities (p 0.01). Complication rates and mortality (0 vs. 0.2%) did not differ significantly. Adolescents achieved a BMI reduction of 16.8 and 18.0 kg/mLSG is a safe therapeutic option that can be performed in adolescents without mortality. Late adolescents experienced the highest weight loss; resolution rate of comorbidities was lower in adults. All future efforts should now be focused on the evaluation of the long-term outcomes of LSG in the pediatric population.

PURPOSE Our aim was to assess the prognostic and predictive value of somatostatin receptor 2 (sstr2) in neuroendocrine tumors (NETs). METHODS We established a tissue microarray and imaging database from NET patients that received sstr2-targeted radiopeptide therapy with yttrium-90-DOTATOC, lutetium-177-DOTATOC or alternative treatment. We used univariate and multivariate analyses to identify prognostic and predictive markers for overall survival, including sstr2-imaging and sstr2-immunohistochemistry. RESULTS We included a total of 279 patients. In these patients, sstr2-immunohistochemistry was an independent prognostic marker for overall survival (HR: 0.82, 95 % CI: 0.67 - 0.99, n = 279, p = 0.037). In DOTATOC patients, sstr2-expression on immunohistochemistry correlated with tumor uptake on sstr2-imaging (n = 170, p

Background and Purpose— In computed tomographic imaging of acute intracerebral hemorrhage spot sign on computed tomographic angiography has been established as a marker for hematoma expansion and poor clinical outcome. Although, magnetic resonance imaging (MRI) can accurately visualize acute intracerebral hemorrhage, a corresponding MRI marker is lacking to date. Methods— We prospectively examined 50 consecutive patients with acute intracerebral hemorrhage within 24 hours of symptom onset. The MRI protocol consisted of a standard stroke protocol and dynamic contrast-enhanced T1-weighted imaging with a time resolution of 7.07 s/batch. Stroke scores were assessed at admission and at time of discharge. Volume measurements of hematoma size and spot sign were performed with MRIcron. Results— Contrast extravasation within sites of the hemorrhage (MRI spot sign) was seen in 46% of the patients. Patients with an MRI spot sign had a significantly shorter time to imaging than those without ( P P ≤0.001). Hematoma expansion was observed in the spot sign group compared with the nonspot sign group, although the differences were not significant. Conclusions— Spot sign can be detected using MRI on postcontrast T1-weighted and dynamic T1-weighted images. It is associated with worse clinical outcome. The time course of contrast extravasation in dynamic T1 images indicates that these spots represent ongoing bleeding.

Background: In the SQUIRE study, adding the anti-epidermal growth factor receptor (EGFR) IgG1 antibody necitumumab to first-line gemcitabine and cisplatin (GC + N) in advanced squamous non-small-cell lung cancer (sqNSCLC) significantly improved overall survival (OS); the safety profile was acceptable. We explored data for the German subpopulation (N = 96) of SQUIRE patients with EGFR-expressing tumors. Patient and Methods: Patients with stage IV sqNSCLC were randomized 1:1 to up to 6 cycles of open-label GC + N or GC alone. GC + N patients with no progression continued on necitumumab monotherapy until disease progression or intolerable toxicity. The primary endpoint was OS; the secondary endpoints included progression-free survival (PFS), safety and health-related quality of life (EQ-5D, Lung Cancer Symptom Scale (LCSS)). Results: The 96 German SQUIRE patients with EGFR-expressing tumors (GC + N 42, GC 54) received a median of 4 GC cycles; the GC + N patients received 5 cycles of necitumumab. Adding necitumumab was associated with 41% risk reduction of death (hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.37-0.94, p = 0.026) and 44% risk reduction of progression (HR 0.56, 95% CI 0.33-0.95, p = 0.029). Adverse events typically associated with EGFR antibody treatment (including rash, hypomagnesemia) were more common with GC + N. The time to deterioration of the EQ-5D and LCSS scores showed no notable differences between the treatment arms, except for appetite loss (delayed for GC + N). Conclusion: The survival benefit from adding necitumumab to first-line GC was more pronounced in the German SQUIRE subpopulation with EGFR-expressing tumors than in the overall (intention-to-treat) population; toxicity was manageable and consistent with the overall population.

Approximately 20% of patients suffering from stroke with pure or predominant sensory symptoms (referred to as sensory stroke patients) develop central poststroke pain (CPSP). It is largely unknown what distinguishes these patients from those who remain pain free. Using quantitative sensory testing (QST), we analyzed the somatosensory profiles of 50 patients with chronic sensory stroke, of which 25 suffered from CPSP. As compared with reference data from healthy controls, patients with CPSP showed alterations of thermal and mechanical thresholds on the body area contralateral to their stroke (P < 0.01). Patients with sensory stroke but without CPSP (non-pain sensory stroke [NPSS] patients) exhibited similar albeit less pronounced contralesional changes. Paradoxical heat sensation (PHS) and dynamic mechanical allodynia (DMA) showed higher values in CPSP, and an elevated cold detection threshold (CDT) was seen more often in CPSP than in patients with NPSS (P < 0.05). In patients with CPSP, changes in CDT, PHS, dynamic mechanical allodynia, and temporal pain summation (wind-up ratio) each correlated with the presence of pain (P < 0.05). On the homologous ipsilesional body area, both patient groups showed additional significant abnormalities as compared with the reference data, which strongly resembled the contralesional changes. In summary, our analysis reveals that CPSP is associated with impaired temperature perception and positive sensory signs, but differences between patients with CPSP and NPSS are subtle. Both patients with CPSP and NPSS show considerable QST changes on the ipsilesional body side. These results are in part paralleled by recent findings of bilaterally spread cortical atrophy in CPSP and might reflect chronic maladaptive cortical plasticity, particularly in patients with CPSP.

ZusammenfassungDiese Handlungsempfehlung soll eine Grundlage für die Qualitätssicherung der Radionuklidtherapie von Knochenmetastasen mit Radium-223 schaffen. Sie wurde interdisziplinär erarbeitet und beschreibt die allgemeine Zielsetzung, Definitionen und klinischen Hintergrundinformationen sowie Indikationen und Kontraindikationen dieser Radionuklidtherapie. Ausgeführt werden die Anforderungen, die an ein Behandlungszentrum gestellt werden, prätherapeutisch notwendige Untersuchungsbefunde sowie Empfehlungen, wie die Behandlung technisch und organisatorisch durchgeführt werden sollte. Ferner finden sich Angaben zur Kontrolle und Nachsorge der therapierten Patienten. Grundsätzlich sollen Behandlung und Nachsorge in Abstimmung und Zusammenarbeit der beteiligten Fachdisziplinen erfolgen.

Background The VEDOibd I study is an investigator initiated, ongoing, non-interventional trial on biologics in IBD-patients (Crohn′s disease (CD) and ulcerative colitis (UC)) in Germany with consecutive recruitment and prospective documentation of effectiveness in induction and maintenance therapy of biologics, especially vedolizumab (VEDO). The aim of this analysis was to compare steroid-free remission rates in CD- and UC-patients after a 14-week-long induction phase of VEDO (bio-naïve and bio-experienced) vs. other biologics (infliximab (IFX), adalimumab (ADA), Golimumab (GLM), Ustekinumab (UST)) in bio-naïve patients. Methods From 10/2017 to 07/2019 750 IBD-patients (CD: 414; UC: 336) from 45 gastroenterology practices and hospitals with IBD-experience from all over Germany were recruited in the VEDOibd I study of whom 232 CD- and 184 UC-patients completed induction phase (week 14) in this interim analysis. At week 14 we compared clinical response (CD: reduction of Harvey Bradshaw Index [HBI] from baseline to week 14 by >3 points or HBI < 4 in week 14; UC: reduction of partial Mayo score [pMayo] from baseline to week 14 by >3 points or a reduction of at least 30% compared with baseline) and steroid-free remission rates (CD: HBI < 4 and no systemic use of steroids or budesonide at week 14; UC: pMayo ≤1 plus a bleeding subscore = 0 and no systemic use of steroids or budesonide at week 14) in patients with VEDO vs. other biologics. Results Ninety-two CD- and 111 UC-patients started a first-time VEDO therapy; of these 40 CD- (43%) and 57 UC-patients (51%) were bio-naïve. Furthermore 140 CD-patients (IFX 48.6%; ADA 47.1%; UST 4.3%) and 73 UC-patients (IFX 58.9%; ADA 24.7%; GLM 16.4%) started treatment with another biologic than VEDO and all of these were bio-naïve. Baseline characteristics were well balanced between both naïve groups (VEDO/other biologics; p > 0.05): males [%]: CD 38/41, UC 37/51; age [years]: CD 46 ± 15/42 ± 15, UC 43 ± 19/39 ± 15; disease duration [years]: CD 15 ± 11/9 ± 11, UC 9 ± 9/6 ± 7; extraintestinal manifestations [%]: CD 23/20, UC 7/15. Response/steroid-free remission rates after induction phase in biologic-naïve patients with VEDO and other biologics were 74.4%/57.5% vs. 78.4%/64.3% in CD (p>0.05) and 60.0%/21.1% vs. 56.0%/13.7% in UC (p>0.05), respectively. Conclusion In this real-world setting we could show that in CD the effectiveness of VEDO vs. other biologics was very similar in bio-naïve patients and that in UC patients, VEDO treatment tended to be numerically superior to other biologics with respect to response and steroid-free remission rates. Further follow-up data of this interim-analysis including the whole planned study population of 1.200 IBD-patients will be shown in the near future.

Pregnancy outcomes in IBD patients treated with vedolizumab, anti-TNF, or conventional therapy

Background and Aims: In Crohn's disease (CD) patients still remain refractory to current regimens, including biologicals. Previous data from small single-center studies indicated cyclophosphamide pulse therapy (CPT) to be effective for induction of remission at least in steroid-refractory cases. The aim of the present study was to study the efficacy and safety of CPT in mainly tumor necrosis factor (TNF)-refractory complicated CD patients. Methods: Patients with refractory CD undergoing CPT were identified in 13 centers of the German IBD Study Group and retrospectively registered. In total, 41 patients (12 male, 29 female, median age 36 years, range 18-72 years) were included for analysis. Seventy-eight percent of these had previously been treated with thiopurines and 90% had previously received anti-TNF antibodies. Former steroid treatment was found throughout the cohort. Results: Patients received a median number of 5 (1-13) pulses every 28 (13-54) days in a period of 120 (12-411) days. A median dose of 766 (600-1,200) mg and a median cumulative dose of 4,500 (750-9,750) mg was given. A clinical response (reduction in the Harvey-Bradshaw Index [HBI] ≥2 points) was found in 68% of the patients and clinical remission (HBI n = 29) of the patients. Three patients terminated CPT due to side effects. No patient died. Conclusion: Our data point to CPT as a therapeutic alternative for induction of remission in patients with severe refractory courses of CD including TNF antagonists. CPT might serve as bridging for maintenance treatment.

Purpose To determine the thyroid clearance effective half-life T with a common handheld electronic dosimeter (ED) in patients undergoing radioiodine treatment for hyperthyroidism. Methods Dose rates from 12 inpatients were measured daily with an ED and with a clinical uptake counter. The ED was attached to the patient with two different setups, one using a cervical collar and another employing a neck strap. Estimation of T was performed by linear regression analysis of the log of both the ED and the uptake counter measurements versus time. The latter provided the reference data. Results Based on repeated neck strap dose rate measurements, individual Ts were determined with clinically required accuracy. The mean difference from the reference method equaled to -0.09 ± 0.35 days. Conclusions Determination of individual T is feasible with a common handheld ED using the simple and easy to instruct neck strap measurement setup. This simple method complements stationary uptake counter measurements and thus may improve the accuracy of radioiodine treatment planning by adding an individual T for dose calculation.

It has been proposed that cortical structural plasticity plays a crucialrole in the emergence and maintenance of chronic pain. Various dis-tinct pain syndromes have accordingly been linked to specific pat-terns of decreases in regional gray matter volume (GMV). However, itis not known whether central poststroke pain (CPSP) is also asso-ciated with cortical structural plasticity. To determine this, we em-ployed T1-weighted magnetic resonance imaging at 3 T and voxel-based morphometry in 45 patients suffering from chronic subcorticalsensory stroke with (n = 23) and without CPSP (n = 22), andhealthy matched controls (n = 31). CPSP patients showed decreasesin GMV in comparison to healthy controls, involving secondary som-atosensory cortex (S2), anterior as well as posterior insular cortex,ventrolateral prefrontal and orbitofrontal cortex, temporal cortex,and nucleus accumbens. Comparing CPSP patients to nonpain pa-tients revealed a similar but more restricted pattern of atrophy com-prising S2, ventrolateral prefrontal and temporal cortex. Additionally,GMV in the ventromedial prefrontal cortex negatively correlated topain intensity ratings. This shows for the first time that CPSP is ac-companied by a unique pattern of widespread structural plasticity,which involves the sensory-discriminative areas of insular/somato-sensory cortex, but also expands into prefrontal cortex and ventralstriatum, where emotional aspects of pain are processed.

BACKGROUND: Mirror therapy (MT) was found to improve motor function after stroke, but its neural mechanisms remain unclear, especially in single stroke patients. OBJECTIVES: The following imaging study was designed to compare brain activation patterns evoked by the mirror illusion in single stroke patients with normal subjects. METHODS: Fifteen normal volunteers and five stroke patients with severe arm paresis were recruited. Cerebral activations during movement mirroring by means of a video chain were recorded with functional magnetic resonance imaging (fMRI). Single-subject analysis was performed using SPM 8. RESULTS: For normal subjects, ten and thirteen subjects displayed lateralized cerebral activations evoked by the mirror illusion while moving their right and left hand respectively. The magnitude of this effect in the precuneus contralateral to the seen hand was not dependent on movement speed or subjective experience. Negative correlation of activation strength with age was found for the right hand only. The activation pattern in stroke patients is comparable to that of normal subjects and present in four out of five patients. CONCLUSIONS: In summary, the mirror illusion can elicit cerebral activation contralateral to the perceived hand in the majority of single normal subjects, but not in all of them. This is similar even in stroke patients with severe hemiparesis.

SummaryThe technical developments that have taken place in the preceding years (PET, hybrid imaging) have changed nuclear medicine. The future cooperation with radiologists will be challenging as well as positioning nuclear medicine in an European context. It can also be expected that education in nuclear medicine will undergo a harmonization process in the states of the European Union.In this paper, we describe how nuclear medicine education is organized in several European countries. We aim to stimulate constructive discussions on the future development of the specialization in nuclear medicine in Germany.

Percutaneous needle intervention based on PET/CT images is effective, but exposes the patient to unnecessary radiation due to the increased number of CT scans required. Computer assisted intervention can reduce the number of scans, but requires handling, matching and visualization of two different datasets. While one dataset is used for target definition according to metabolism, the other is used for instrument guidance according to anatomical structures. No navigation systems capable of handling such data and performing PET/CT image-based procedures while following clinically approved protocols for oncologic percutaneous interventions are available. The need for such systems is emphasized in scenarios where the target can be located in different types of tissue such as bone and soft tissue. These two tissues require different clinical protocols for puncturing and may therefore give rise to different problems during the navigated intervention. Studies comparing the performance of navigated needle interventions targeting lesions located in these two types of tissue are not often found in the literature. Hence, this paper presents an optical navigation system for percutaneous needle interventions based on PET/CT images. The system provides viewers for guiding the physician to the target with real-time visualization of PET/CT datasets, and is able to handle targets located in both bone and soft tissue. The navigation system and the required clinical workflow were designed taking into consideration clinical protocols and requirements, and the system is thus operable by a single person, even during transition to the sterile phase. Both the system and the workflow were evaluated in an initial set of experiments simulating 41 lesions (23 located in bone tissue and 18 in soft tissue) in swine cadavers. We also measured and decomposed the overall system error into distinct error sources, which allowed for the identification of particularities involved in the process as well as highlighting the differences between bone and soft tissue punctures. An overall average error of 4.23 mm and 3.07 mm for bone and soft tissue punctures, respectively, demonstrated the feasibility of using this system for such interventions. The proposed system workflow was shown to be effective in separating the preparation from the sterile phase, as well as in keeping the system manageable by a single operator. Among the distinct sources of error, the user error based on the system accuracy (defined as the distance from the planned target to the actual needle tip) appeared to be the most significant. Bone punctures showed higher user error, whereas soft tissue punctures showed higher tissue deformation error.

Die Positronen-Emissions-Tomographie (PET) hat sich während der letzten 20 Jahre zum diagnostischen Goldstandard in der Bildgebung einer Mehrzahl von malignen Tumorerkrankungen entwickelt, darunter insbesondere für die bildgebende Untersuchung von Patienten mit malignen Lymphomen. Mit der Entwicklung und Verbreitung von sogenannten Hybridgeräten, die gleichzeitig eine PET-Untersuchung und eine Computertomographie (CT) ermöglichen, und die mit Hilfe fusionierter PET/CT Bilder auch kleinste krankhafte Prozesse zuverlässig zuordnen lassen, wurde die Wertigkeit der Methode nochmals erheblich verbessert. Die hohe Empfindlichkeit der Stoffwechselbildgebung mit PET bzw. PET/CT ermöglicht eine zuverlässige Gesamtbeurteilung von Patienten mit malignen Lymphom für die Stadieneinteilung vor Therapiebeginn, die frühe Diagnose von Therapieversagern unter Therapie sowie das sichere Erkennen von Rezidiven nach Therapie.

Positron emission tomography-computed tomography (PET-CT) has gained widespread acceptance as a staging investigation in the diagnostic workup of malignant tumours and may be used to visualize metabolic changes before the evolution of morphological changes. To make histology of PET findings without distinctive structural changes available for treatment decisions, we developed a protocol for multimodal image-guided interventions using an integrated PET-CT machine. We report our first experience in 12 patients admitted for staging and restaging of breast cancer, non-small cell lung cancer, cervical cancer, soft tissue sarcoma, and osteosarcoma. Patients were repositioned according to the findings in PET-CT and intervention was planned based on a subsequent single-bed PET-CT acquisition of the region concerned. The needle was introduced under CT guidance in a step-by-step technique and correct needle position in the centre of the FDG avid lesion was assured by repetition of a single-bed PET-CT acquisition before sampling. The metabolically active part of lesions was accurately targeted in all patients and representative samples were obtained in 92%. No major adverse effects occurred. We conclude that PET-CT guidance for interventions is feasible and may be promising to optimize the diagnostic yield of CT-guided interventions and to make metabolically active lesions without morphological correlate accessible to percutaneous interventions.

BACKGROUND: Constipation is a significant side effect of opioid therapy. We have previously demonstrated that naloxone-3-glucuronide (NX3G) antagonizes the motility-lowering-effect of morphine in the rat colon. AIM: To find out whether oral NX3G is able to reduce the morphine-induced delay in colonic transit time (CTT) without being absorbed and influencing the analgesic effect. METHODS: Fifteen male volunteers were included. Pharmacokinetics: after oral administration of 0.16 mg/kg NX3G, blood samples were collected over a 6-h period. Pharmacodynamics: NX3G or placebo was then given at the start time and every 4 h thereafter. Morphine (0.05 mg/kg) or placebo was injected s.c. 2 h after starting and thereafter every 6 h for 24 h. CTT was measured over a 48-h period by scintigraphy. Pressure pain threshold tests were performed. RESULTS: Neither NX3G nor naloxone was detected in the venous blood. The slowest transit time was observed during the morphine phase, which was significantly different from morphine with NX3G and placebo. The pain perception was not significantly influenced by NX3G. CONCLUSIONS: Orally administered NX3G is able to reverse the morphine-induced delay of CTT in humans without being detected in peripheral blood samples. Therefore, NX3G may improve symptoms of constipation in-patients using opioid medication without affecting opioid-analgesic effects.

Objectives Lymph node status is an important prognostic factor in patients with squamous cell carcinoma (SCC) of the vulva. Complete inguinofemoral lymph node dissection (ILND) is accompanied by a high morbidity. Sentinel lymph node biopsy (SLNB) was established for less invasive lymph node (LN) staging. The aim of this study was to evaluate safety of SLNB in terms of accuracy and outcome in a clinical routine setting. Methods We retrospectively reviewed the data of patients who underwent SLNB and/or ILND for vulvar SCC in the years 1990–2007. Clinical follow-up was evaluated for histological nodal-negative patients with tumor stage T1 or T2. The false negative rate of SLNB was determined in patients who underwent both SLNB and ILND. Results Preoperative sentinel lymph node (SLN) visualization by scintigraphy was successful in 95% of all patients. SLNB was false negative in 1/45 inguinae (2.2%). All SLN were detected intraoperatively. During the follow-up period (median 24 months for SLNB and 111 months for ILND), no groin recurrences in initially nodal negative patients occurred ( n =34, 59 inguinae). Transient lymph edema occurred in 7/18 patients after ILND (39%) and 2/16 patients (13%) after SLNB. No persistent edemas were found after SLNB and ILND. Conclusion According to our experience SLNB is feasible and accurately predicts LN status of vulvar SCC under clinical routine conditions. SLNB in vulvar cancer seems to be a safe alternative to ILND in order to reduce morbidity of surgical treatment.

Objective To investigate the usefulness of presurgical image fusion of three-dimensional single photon emission computed tomography (SPECT) with computed tomography/magnetic resonance imaging (CT/MRI) for detecting primary prostatic lymphatic landing sites (sentinel lymph nodes [SLNs]) using an intraoperative γ probe in patients undergoing radical prostatectomy for organ-confined prostate cancer after intraprostatic 99m Tc-nanocolloid injection. Methods In 15 patients the surgeon was unaware of the preoperative SPECT/CT/MRI fusion imaging results. In 21 patients the surgeon was supported by the preoperative SPECT/CT/MRI images. Selective SLN resection was followed by an extended backup pelvic lymph node dissection (PLND) and radical prostatectomy. Results In the group of 15 patients (γ probe-guided SLN search only) presurgical SPECT/CT/MRI identified 137 SLNs (median of 10/patient; range: 2–19) and a total of 135 SLNs (median of 8/patient; range: 2–20) were detected intraoperatively (detection rate 98.5%). In the group of 21 patients with the surgeon knowing the preoperative SPECT/CT/MRI findings, 189 (median of 9/patient; range: 3–20) of the 190 imaged SLNs (median of 8/patient, range: 2–19) were found intraoperatively (detection rate 99.5%). Median operating time for sentinel lymphadenectomy using γ probe only was 100min (range: 40–130) versus 70min (range: 20–140) for the SPECT/CT/MRI-supported resection ( p =0.025). A median of 9 SLNs per patient (range: 2–19) was confirmed histologically. Conclusions Preoperative SPECT/CT/MRI is highly reliable to detect nonmetastatic sentinel nodes of the prostate. The operating time for SPECT/CT/MRI-supported SLN resection is significantly reduced compared to SLN resection guided by γ probe alone. Both procedures take significantly longer than routine extended PLND.

Targeted diagnosis and therapy enable precise tumor detection and treatment. Successful examples for precise tumor targeting are diagnostic and therapeutic radioligands. However, patients with tumors expressing low levels of the relevant molecular targets are deemed ineligible for such targeted approaches. Methods: We performed a screen for drugs that upregulate the somatostatin receptor subtype 2 (sstr2). Then, we characterized the effects of these drugs on transcriptional, translational, and functional levels in vitro and in vivo. Results: We identified 9 drugs that act as epigenetic modifiers, including the inhibitor of DNA methyltransferase decitabine as well as the inhibitors of histone deacetylase tacedinaline and romidepsin. In vitro, these drugs upregulated sstr2 on transcriptional, translational, and functional levels in a time- and dose-dependent manner. Thereby, their combinations revealed synergistic effects. In vivo, drug-based sstr2 upregulation improved the tumor-to-background and tumor-to-kidney ratios, which are the key determinants of successful sstr2-targeted imaging and radiopeptide therapy. Conclusion: We present an approach that uses epigenetic modifiers to improve sstr2 targeting in vitro and in vivo. Translation of this method into the clinic may potentially convert patients ineligible for targeted imaging and therapy to eligible candidates.

Survivors of prolonged cerebral anoxia often remain in the persistent vegetative state (PVS). In this study, long-term PVS patients were investigated by 15O-H(2)O PET to analyze their central processing of pain. The study was approved by the local Ethics Committee, the experiments were performed in accordance with the Helsinki Declaration of 2000. Seven patients remaining in PVS of anoxic origin for a mean of 1.6 years (range 0.25-4 years) were investigated. We performed functional PET of the brain using 15O-labelled water during electrical nociceptive stimulation. Additionally, a brain metabolism study using 18F-fluorodeoxyglucose (FDG) PET and multi-sequence MRI (including a 3-D data set) were acquired in all patients. PET data were analyzed by means of Statistical Parametric Mapping (SPM99) and coregistered to a study-specific brain template. MRI and FDG PET showed severe cortical impairment at the structural and the functional level, that is, general atrophy of various degrees and a widespread significant hypometabolism, respectively. Pain-induced activation (hyperperfusion) was found in the posterior insula/secondary somatosensory cortex (SII), postcentral gyrus/primary somatosensory cortex (SI), and the cingulate cortex contralateral to the stimulus and in the posterior insula ipsilateral to the stimulus (P

Cerebral positron emission tomography (PET) in children often requires sedation. This study evaluated sedation-associated effects on cerebral glucose metabolism in 30 children with severe myoclonic epilepsy as investigated by cerebral (18)F-fluorodeoxyglucose (FDG)-PET. Prior to the PET acquisition, 24 children underwent propofol sedation. Pixel-based t-statistics were calculated using statistical parametric mapping (SPM99) for comparisons of the patients' PET scans with both a healthy adult control group and an age-matched child intra-group control. In both analyses, statistically significant hypometabolic areas were found in the medial parieto-occipital cortex bilaterally, including the lingual gyrus, cuneus, posterior cingulate and middle occipital gyrus in all sedated children. All these localizations correlated in a covariate analysis with the injected dose of propofol (P

We performed a multicenter study to determine whether transabdominal bowel wall ultrasonography, a noninvasive procedure that does not require radiation, can be used to monitor progression of Crohn's disease (CD).We performed a 12-month prospective, noninterventional study at 47 sites in Germany, from December 2010 through September 2014. Our study included 234 adult patients with CD who experienced a flare, defined as Harvey-Bradshaw index score of ≥7. All patients received treatment intensification, most with tumor necrosis factor antagonists. Ultrasound parameters and clinical data were assessed at baseline and then after 3, 6, and 12 months. The primary endpoint was the change in ultrasound parameters within 12 months of study enrollment.All patients included had bowel wall alterations either within the terminal ileum and/or segments of the colon. After 3 and 12 months, ultrasonographic examination showed significant improvements of nearly all ultrasound parameters, including reductions in bowel wall thickening or stratification, decreased fibrofatty proliferation, and increased signals in color Doppler ultrasound (P.01 for all parameters at months 3 and 12). Median Harvey-Bradshaw index scores decreased from 10 at baseline to 2 after 12 months. Improvement in bowel wall thickness correlated with reduced levels of C-reactive protein after 3 months (P ≤ .001).In a multicenter prospective study, we found that ultrasonographic examination can be used to monitor disease activity in patients with active CD. Bowel ultrasonography seems to be an ideal follow-up method to evaluate early transmural changes in disease activity, in response to medical treatment. German Clinical Trials Register: drks.de/DRKS00010805.

Functional magnetic resonance imaging (fMRI) was used to examine the influence of non-painful electrical stimulus intensity on the BOLD response in human primary somatosensory cortex (SI). In ten healthy subjects, index and middle finger of the right hand were stimulated separately at two different stimulus intensities. The activated volume of single finger representations as well as the volume of representational overlap of the two activations increased following an increase in stimulus intensity. This effect was seen in two different subdivisions of SI, one in the depth of the central sulcus, presumably corresponding to Brodmann area (BA) 3b, and one on the crown of the postcentral gyrus, presumably corresponding to BA 1/2. Relative overlap (ratio of overlap volume to volume of individual finger representation) was larger in BA 1/2 than in BA 3b. Additionally, in both areas relative overlap increased significantly from low to high stimulus intensity. Relative overlap did not change when different correlation thresholds were employed arguing against an unspecific 'spillover effect'. Analysis of signal intensity time courses indicated that the response difference to high versus low stimulus strength was not present during the initial seconds of stimulation, during which both led to a similar signal intensity increase. Only during the following maintenance level of the response did the response to high stimulus intensity reach a significantly higher plateau level than the one due to low intensity stimulation, an effect which was present in both areas, BA 3b and BA 1/2, respectively.

Bone pain after transplantation is a frequent complication that can be caused by several diseases. Treatment strategies depend on the correct diagnosis of the pain. Nine patients with severe pain in their feet, which was registered after transplantation, were investigated. Bone scans showed an increased tracer uptake of the foot bones. Magnetic resonance imaging demonstrated bone marrow oedema in the painful bones. Pain was not explained by other diseases causing foot pain, like reflex sympathetic dystrophy, polyneuropathy, Morton's neuralgia, gout, osteoporosis, avascular necrosis, intermittent claudication, orthopaedic foot deformities, stress fractures, and hyperparathyroidism. The reduction of cyclosporine- or tacrolimus trough levels and the administration of calcium channel blockers led to relief of pain. The Calcineurin-inhibitor Induced Pain Syndrome (CIPS) is a rare but severe side effect of cyclosporine or tacrolimus and is accurately diagnosed by its typical presentation, magnetic resonance imaging and bone scans. Incorrect diagnosis of the syndrome will lead to a significant reduction of life quality in patients suffering from CIPS.

Angiotensin II is known to stimulate cardiac hypertrophy and contractility. Most angiotensin II effects are mediated via membrane bound AT1 receptors. However, the role of myocardial AT1 receptors in cardiac hypertrophy and contractility is still rarely defined. To address the hypothesis that increased myocardial AT1 receptor density causes cardiac hypertrophy apart from high blood pressure we developed a transgenic rat model which expresses the human AT1 receptor under the control of the alpha-myosin heavy-chain promoter specifically in the myocardium. Expression was identified and quantified by northern blot analysis and radioligand binding assays, demonstrating overexpression of angiotensin II receptors in the transgenic rats up to 46 times the amount seen in nontransgenic rats. Coupling of the human AT1 receptor to rat G proteins and signal transduction cascade was verified by sensitivity to GTP-gamma-S and increased sensitivity of intracellular Ca2+ [Ca2+]i to angiotensin II in fluo-3 loaded transgenic cardiomyocytes. Transgenic rats exhibited normal cardiac growth and function under baseline conditions. Pronounced hypertrophic growth and contractile responses to angiotensin II, however, were noted in transgenic rats challenged by volume and pressure overload. In summary, we generated a new transgenic rat model that exhibits an upregulated myocardial AT1 receptor density and demonstrates augmented cardiac hypertrophy and contractile response to angiotensin II after volume and pressure overload, but not under baseline conditions.