SARS-CoV-2 Test-to-Stay in Daycare.

BACKGROUND AND OBJECTIVES: Test-to-stay concepts apply serial testing of children in daycare after exposure to SARS-CoV-2 without use of quarantine. This study aims to assess the safety of a test-to-stay screening in daycare facilities. METHODS: 714 daycare facilities and approximately 50 000 children ≤6 years in Cologne, Germany participated in a SARS-CoV-2 Pool-polymerase chain reaction (PCR) screening from March 2021 to April 2022. The screening initially comprised post-exposure quarantine and was adapted to a test-to-stay approach during its course. To assess safety of the test-to-stay approach, we explored potential changes in frequencies of infections among children after the adaptation to the test-to-stay approach by applying regression discontinuity in time (RDiT) analyses. To this end, PCR-test data were linked with routinely collected data on reported infections in children and analyzed using ordinary least squares regressions. RESULTS: 219 885 Pool-PCRs and 352 305 Single-PCRs were performed. 6440 (2.93%) Pool-PCRs tested positive, and 17 208 infections in children were reported. We estimated that during a period of 30 weeks, the test-to-stay concept avoided between 7 and 20 days of quarantine per eligible daycare child. RDiT revealed a 26% reduction (Exp. Coef: 0.74, confidence interval 0.52-1.06) in infection frequency among children and indicated no significant increase attributable to the test-to-stay approach. This result was not sensitive to adjustments for 7-day incidence, season, SARS-CoV-2 variant, and socioeconomic status. CONCLUSIONS: Our analyses provide evidence that suggest safety of the test-to-stay approach compared with quarantine measures. This approach offers a promising option to avoid use of quarantine after exposure to respiratory pathogens in daycare settings.

90K/LGALS3BP expression is upregulated in COVID-19 but may not restrict SARS-CoV-2 infection.

Glycoprotein 90K, encoded by the interferon-stimulated gene LGALS3BP, displays broad antiviral activity. It reduces HIV-1 infectivity by interfering with Env maturation and virion incorporation, and increases survival of Influenza A virus-infected mice via antiviral innate immune signaling. Its antiviral potential in SARS-CoV-2 infection remains largely unknown. Here, we analyzed the expression of 90K/LGALS3BP in 44 hospitalized COVID-19 patients at multiple levels. We quantified 90K protein concentrations in serum and PBMCs as well as LGALS3BP mRNA levels. Complementary, we analyzed two single cell RNA-sequencing datasets for expression of LGALS3BP in respiratory specimens and PBMCs from COVID-19 patients. Finally, we analyzed the potential of 90K to interfere with SARS-CoV-2 infection of HEK293T/ACE2, Calu-3 and Caco-2 cells using authentic virus. 90K protein serum concentrations were significantly elevated in COVID-19 patients compared to uninfected sex- and age-matched controls. Furthermore, PBMC-associated concentrations of 90K protein were overall reduced by SARS-CoV-2 infection in vivo, suggesting enhanced secretion into the extracellular space. Mining of published PBMC scRNA-seq datasets uncovered monocyte-specific induction of LGALS3BP mRNA expression in COVID-19 patients. In functional assays, neither 90K overexpression in susceptible cell lines nor exogenous addition of purified 90K consistently inhibited SARS-CoV-2 infection. Our data suggests that 90K/LGALS3BP contributes to the global type I IFN response during SARS-CoV-2 infection in vivo without displaying detectable antiviral properties in vitro.

Spectral Computed Tomography-Derived Iodine Content and Tumor Response in the Follow-Up of Neuroendocrine Tumors-A Single-Center Experience.

Spectral computed tomography (SCT) allows iodine content (IC) calculation for characterization of hypervascularized neoplasms and thus might help in the staging of neuroendocrine tumors (NETs). This single-center prospective study analyzed the association between SCT-derived IC and tumor response in the follow-up of metastasized NETs. Twenty-six patients with a median age of 70 years (range 51-85) with histologically proven NETs and a total of 78 lesions underwent SCT for staging. Because NETS are rare, no primary NET types were excluded. Lesions and intralesional hotspots were measured in virtual images and iodine maps. Tumor response was classified as progressive or nonprogressive at study endpoint. Generalized estimating equations served to estimate associations between IC and tumor response, additionally stratified by lesion location. Most commonly affected sites were the lymph nodes, liver, pancreas, and bones. Median time between SCT and endpoint was 64 weeks (range 5-260). Despite statistical imprecision in the estimate, patients with higher IC in lymphonodular metastases had lower odds for disease progression (adjusted OR = 0.21, 95% CI: 0.02-2.02). Opposite tendencies were observed in hepatic and pancreatic metastases in unadjusted analyses, which vanished after adjusting for therapy and primary tumor grade.

Long-term follow-up of surgical intervention pattern in pediatric low-grade gliomas: report from the German SIOP-LGG 2004 cohort.

OBJECTIVE: Neurosurgical treatment is an integral part of the treatment algorithms for pediatric low-grade glioma (LGG), yet patterns of surgical procedures are rarely challenged. The objective of this study was to evaluate surgical treatment patterns in pediatric LGG. METHODS: The German Societé Internationale d'Oncologie Pédiatrique (SIOP)-LGG 2004 cohort was analyzed to identify relevant patient and tumor characteristics associated with time to death, next surgery, number of resections, and radiological outcome. RESULTS: A total of 1271 patients underwent 1713 neurosurgical interventions (1 intervention in 947, 2 in 230, 3 in 70, and 4-6 in 24). The median age of the study population was 8.57 years at first surgery, and 46.1% were female. Neurofibromatosis type 1 (NF1) was found in 4.4%, and 5.4% had tumor dissemination. Three hundred fifty-four patients (27.9%) had chemotherapy and/or radiotherapy. The cumulative incidence of second surgery at 10 years was 26%, and was higher for infants, those with spinal and supratentorial midline (SML) tumors, and those with pilomyxoid astrocytomas. The hazard ratio for subsequent surgery was higher given dissemination and noncomplete initial resection, and lower for caudal brainstem and SML tumors. Among 1225 patients with fully documented surgical records and radiological outcome, 613 reached complete remission during the observation period, and 50 patients died. Patients with pilocytic astrocytoma had higher chances for a final complete remission, whereas patients with initial partial or subtotal tumor resection, dissemination, NF1, or primary tumor sites in the spinal cord and SML had lower chances. CONCLUSIONS: Neurosurgery is a key element of pediatric LGG treatment. In almost 50% of the patients, however, at least some tumor burden will remain during long-term follow-up. This study found that most of these patients reached a stable disease status without further surgeries. Multidisciplinary team decisions must balance the goal of complete resection, risk factors, repeated surgeries, and possible treatment alternatives in a wide range of heterogeneous entities. Procedural details and neurological outcome should be recorded to better assess their impact on long-term outcome.

Tumor load rather than contrast enhancement is associated with the visual function of children and adolescents with optic pathway glioma - a retrospective Magnetic Resonance Imaging study.

INTRODUCTION: Optic pathway gliomas are often asymptomatic tumors occurring in children with neurofibromatosis type 1 (NF1 + OPG) or sporadically (spOPG). Treatment is usually prompted by visual loss and/or tumor progression on MRI. The aim of this study was to investigate the relationship between visual acuity (VA), tumor growth, and contrast enhancement to provide more distinct indications for the administration of gadolinium-based contrast agents. METHODS: Tumor load was retrospectively measured and enhancement semi-quantitatively scored on 298 MRIs of 35 patients (63% NF1 + OPG). Spearman rank correlation between tumor load and enhancement was calculated and a linear mixed model used to examine the influence of tumor load and enhancement on corresponding VA tests (LogMAR). RESULTS: The optic nerve width in NF1 + OPGs was strongly associated with VA (regression coefficient 0.75; confidence interval 0.61-0.88), but weakly with enhancement (0.06; -0.04-0.15). In spOPGs, tumor volume and optic nerve width were more relevant (0.31; -0.19-0.81 and 0.39; 0.05-0.73) than enhancement (0.09; -0.09-0.27). CONCLUSIONS: Tumor load measures may be more relevant for the surveillance of optic pathway gliomas than enhancement, given that VA is the relevant outcome parameter. Regular contrast administration should therefore be questioned in these patients.

Association Between Neuronal Autoantibodies and Cognitive Impairment in Patients With Lung Cancer.

IMPORTANCE: Paraneoplastic neurological syndromes are associated with neuronal autoantibodies, and some of these autoantibodies are associated with neuropsychological symptoms. The most common underlying tumor is lung cancer. The association of neuronal autoantibodies with cognitive deficits has not been systematically investigated in patients with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). OBJECTIVE: To assess the frequency of neuronal autoantibodies in patients with lung cancer and analyze their association with cognitive function. DESIGN, SETTING, AND PARTICIPANTS: This prospective, cross-sectional study included 167 patients with lung cancer (both SCLC and NSCLC) recruited at a single lung cancer center in Berlin, Germany, between June 2015 and April 2016. Detailed neuropsychological testing was performed in a carefully selected subgroup of 97 patients (from which patients with potential confounding factors were excluded). Investigators were blinded to patients' autoantibody status and cognitive test results. Data were analyzed from May 2016 to December 2019. MAIN OUTCOMES AND MEASURES: Prevalence of neuronal autoantibodies and their association with cognitive impairment. The evaluation of autoantibodies as potential risk factors for cognitive impairment was performed using bayesian logistic regression models. RESULTS: Among 167 patients with lung cancer (median age, 66.0 years [interquartile range, 59.0-72.0 years]; 105 men [62.9%]), 127 had NSCLC, and 40 had SCLC. Brain-directed autoantibodies were detected in 61 of 167 patients (36.5%); 33 patients (19.8%) had known autoantibodies and 28 patients (16.8%) had autoantibodies against currently unknown antigens that were detected through immunohistochemical analysis. Cognitive impairment was found in 65 of 97 patients (67.0%). Among patients with SCLC, the odds of cognitive impairment for those with any autoantibodies was 11-fold higher (odds ratio [OR], 11.0; 95% credible interval [CrI], 1.2-103.6) than that of autoantibody-negative patients, and the increased odds were independent of age, sex, and neurological deficit. Among patients with NSCLC, those with immunoglobin A autoantibodies targeting the N-methyl-d-aspartate receptor had a relevantly increased odds of verbal memory deficits (OR, 182.8; 95% CrI, 3.1-10 852.4). Autoantibodies against currently unknown antigens were also associated with increased odds of cognitive impairment (OR, 2.8; 95% CrI, 0.6-12.1). CONCLUSIONS AND RELEVANCE: In this prospective, cross-sectional study, more than one-third of patients with lung cancer had neuronal autoantibodies that were found to be associated with cognitive impairment. These autoantibodies might represent a potentially treatable mechanism of immune-mediated cognitive impairment among patients with lung cancer.

Relevance of maternal sodium level for preeclampsia-associated adverse pregnancy outcomes.

OBJECTIVE: To evaluate maternal sodium levels in women with preeclampsia (PE) or at high risk for preeclampsia and their relevance for severe PE-associated adverse pregnancy outcome and remaining pregnancy duration. STUDY DESIGN: In a retrospective cohort of 198 patients presenting with signs and symptoms of preeclampsia (PE), we investigated maternal sodium level and the sFlt-1/PlGF-ratio within 14 days prior to delivery. MAIN OUTCOME MEASURES: In total, 88 patients (44.4%) developed a maternal and/or fetal and neonatal preeclampsia-associated adverse outcome (AO). The median sodium level was lower in the cohort with vs. without AO (136 vs. 137 mmol/l) and correlated negatively with the sFlt-1/PlGF-ratio (r = -0.19, 95% CI: -0.31 to -0.05) in both groups. Logistic regression revealed a significant association of the maternal sodium level with the development of an AO (+1 mmol/l reduced the odds by 21%, [Odds ratio (OR) of 0.79 (95% CI 0.67-0.93), p < 0.01], whereas the sFlt-1/PlGF showed a contrary effect (+10 units OR of 1.05 (95% CI: 1.02-1.08, p < 0.01)). Linear mixed effects models showed consistent results, with sodium level positively associated with the remaining pregnancy duration. CONCLUSIONS: Our results confirm the relevance of decreased maternal sodium level as a severity marker for PE-associated adverse outcomes.

Decreased Medical Care During the COVID-19 Pandemic - A Comprehensive Analysis of Radiological Examinations.

OBJECTIVES: As a cross-section discipline within the hospital infrastructure, radiological departments might be able to provide important information regarding the impact of the COVID-19 pandemic on healthcare. The goal of this study was to quantify changes in medical care during the first wave of the pandemic using radiological examinations as a comprehensive surrogate marker and to determine potential future workload. METHODS: A retrospective analysis of all radiological examinations during the first wave of the pandemic was performed. The number of examinations was compared to time-matched control periods. Furthermore, an in-depth analysis of radiological examinations attributed to various medical specialties was conducted and postponed examinations were extrapolated to calculate additional workload in the near future. RESULTS: A total of 596,760 examinations were analyzed. Overall case volumes decreased by an average of 41 % during the shutdown compared to the control period. The most affected radiological modalities were sonography (-54 %), X-ray (-47 %) followed by MRI (-42 %). The most affected medical specialty was trauma and orthopedics (-60 % case volume) followed by general surgery (-49 %). Examination numbers increased during the post-shutdown period leading to a predicted additional workload of up to 22 %. CONCLUSION: This study shows a marked decrease in radiological examinations in total and among several core medical specialties, indicating a significant reduction in medical care during the first COVID-19 shutdown. KEY POINTS: · Number of radiological examinations decreased by 41 % during the first wave of the COVID-19 pandemic.. · Several core medical specialties were heavily affected with a reduction of case volumes up to 60 %.. · When extrapolating postponed examinations to the near future, the overall workload for radiological departments might increase up to 22 %.. CITATION FORMAT: · Fleckenstein FN, Maleitzke T, Böning G et al. Decreased Medical Care During the COVID-19 Pandemic - A Comprehensive Analysis of Radiological Examinations. Fortschr Röntgenstr 2021; 193: 937 - 946.

Methods to estimate proportion and number of nonexposed cases in a population.

National mortality statistics commonly provide disease-specific absolute and relative frequencies of death by sex and age, but not by exposure status. However, it is often of interest to know how many of the diseased individuals, that is the cases, were exposed or not exposed to a specific risk factor. We present two methods to estimate the proportion and the number of exposed and nonexposed cases, both of which require an estimate of the exposure prevalence in the nondiseased population. Method I additionally requires an estimate of the relative effect of exposure, that is a relative risk function if the exposure has a continuous distribution, or a relative risk estimate for each category if the exposure is categorical. Method II additionally requires an estimate of the disease rate among the nonexposed. We provide theoretical justifications, discuss practical limitations, and provide an R script to calculate the probability for nonexposure among the diseased, and compare the approaches. Both methods are subsequently applied to the estimation of the number of never smokers among lung cancer deaths. The two suggested methods rely on the availability of specific data sources and might therefore be applicable in different research settings. Both methods yield unbiased estimates of the number of nonexposed cases, given that the respective underlying assumptions are fulfilled.

Neurodevelopmental outcome at 2 years after neuroendoscopic lavage in neonates with posthemorrhagic hydrocephalus.

OBJECTIVE: A standardized guideline for treatment of posthemorrhagic hydrocephalus in premature infants is still missing. Because an early ventriculoperitoneal shunt surgery is avoided due to low body weight and fragility of the patients, the neurosurgical treatment focuses on temporary solutions for CSF diversion as a minimally invasive approach. Neuroendoscopic lavage (NEL) was additionally introduced for early elimination of intraventricular blood components to reduce possible subsequent complications such as shunt dependency, infection, and multiloculated hydrocephalus. The authors report their first experience regarding neurodevelopmental outcome after NEL in this patient cohort. METHODS: In a single-center retrospective cohort study with 45 patients undergoing NEL, the authors measured neurocognitive development at 2 years with the Bayley Scales of Infant Development, 2nd Edition, Mental Developmental Index (BSID II MDI) and graded the ability to walk with the Gross Motor Function Classification System (GMFCS). They further recorded medication with antiepileptic drugs (AEDs) and quantified ventricular and brain volumes by using 3D MRI data sets. RESULTS: Forty-four patients were alive at 2 years of age. Eight of 27 patients (30%) assessed revealed a fairly normal neurocognitive development (BSID II MDI ≥ 70), 28 of 36 patients (78%) were able to walk independently or with minimal aid (GMFCS 0-2), and 73% did not require AED treatment. Based on MR volume measurements, greater brain volume was positively correlated with BSID II MDI (rs = 0.52, 95% CI 0.08-0.79) and negatively with GMFCS (rs = -0.69, 95% CI -0.85 to -0.42). Based on Bayesian logistic regression, AED treatment, the presence of comorbidities, and also cerebellar pathology could be identified as relevant risk factors for both neurodevelopmental outcomes, increasing the odds more than 2-fold-but with limited precision in estimation. CONCLUSIONS: Neuromotor outcome assessment after NEL is comparable to previously published drainage, irrigation, and fibrinolytic therapy (DRIFT) study results. A majority of NEL-treated patients showed independent mobility. Further validation of outcome measurements is warranted in an extended setup, as intended by the prospective international multicenter registry for treatment of posthemorrhagic hydrocephalus (TROPHY).

Secondary tethered cord syndrome in adult patients: retethering rates, long-term clinical outcome, and the effect of intraoperative neuromonitoring.

BACKGROUND: The strategy for surgical treatment of tethered cord syndrome in pediatric patients is well established but still bares challenges for adult patients. This retrospective study was performed to assess the surgical outcome of adult patients with a secondary tethered cord syndrome and to evaluate the benefit of intraoperative neuromonitoring. METHODS: Clinical charts of 32 consecutive adult patients who underwent in total 38 surgical untethering procedures at our facility between 2008 and 2018 were retrospectively analyzed. Epidemiological data, MRI scans, and postoperative results were evaluated. RESULTS: The retethering rate in our patient cohort was 16%. Main complaints were maximal pain (82%), bladder dysfunction (79%), paresthesia (68%), and weakness in the lower extremities (68%). Forty-eight months after surgery, patients' symptoms generally improved, with an average level of pain of 19.1% (95% CI, 5.7-32.5%), paresthesia 28.7% (95% CI, 12.6-44.8%), weakness in the lower extremities 27.7% (95% CI, 11.1-44.4%), and bladder dysfunction 60.2% (95% CI, 41.6-78.7%). The use of neuromonitoring appears to have a positive impact on patient weakness (OR = 0.07; 95% CI, 0.01-0.68) and paresthesia (OR = 0.03; 95% CI, 0.00-2.18). This benefit is less clear for the retethering rate (OR = 0.45; 95% CI, 0.06-3.26) or the overall clinical outcome (OR = 0.70; 95% CI, 0.14-3.45). The presence of a preoperative Chiari syndrome, syringomyelia, or scoliosis had no relevant influence on the retethering rate. CONCLUSIONS: Our data confirms that untethering surgery in adult patients is relatively safe and has a reasonable chance of clinical improvement of pain, paresthesia, and weakness in the lower extremities. The use of intraoperative monitoring has a positive influence on the improvement of preoperative paralysis.

Population-based study of autoimmune hepatitis and primary biliary cholangitis in Germany: rising prevalences based on ICD codes, yet deficits in medical treatment.

BACKGROUND: Population-based data on the prevalence of and real-life treatment for the autoimmune liver diseases (AILD), primary biliary cholangitis (PBC) and autoimmune hepatitis (AIH), are scarce, and such knowledge may help to improve patient care. METHODS: Data of 8.1 million individuals having health insurance with the "Techniker Krankenkasse," the largest German health insurer, were analyzed with regard to the prevalence of and prescribed medication for AILD in Germany from 2011 until 2014. Patients with viral hepatitis B infection (HBV) and alcoholic liver cirrhosis (ALC) served as control groups. Case definition was based on ICD codes. RESULTS: The prevalences of PBC and AIH were 36.9/100 000 inhabitants (95 % CI: 35.6-38.2) and 23.0/100 000 inhabitants (95 % CI: 22.0-24.0) in 2014, respectively. The prevalences of AILD increased from 2011 to 2014 (for PBC by 31 % and for AIH by 29 %), with the largest increase for male patients with PBC. In contrast, the prevalence of HBV declined while that of ALC remained stable. The analysis of prescribed real-life treatment revealed considerable deviations from standard treatment recommendations. Specifically, in older patients with PBC or AIH, undertreatment was common. CONCLUSION: The prevalence of PBC and AIH based on ICD codes is increasing in Germany. The analysis of real-life treatment in this large and population-based cohort points to the unmet need to improve the implementation of treatment guidelines for autoimmune liver diseases in the broader medical community.

Association of a Multigenetic Pro-Inflammatory Profile with Ischaemic Stroke.

OBJECTIVE: A multigenetic pro-inflammatory profile may increase stroke risk. We investigated whether a higher number of pro-inflammatory genetic variants are associated with ischaemic stroke risk and whether other risk factors further elevate this risk. METHODS: In a case-control study with 470 ischaemic stroke patients (cases) and 807 population controls, we investigated 23 haplotypes or alleles in 16 inflammatory genes (interleukin [IL]1A, IL1B, IL1 receptor antagonist, IL6, IL6 receptor, IL10, tumour necrosis factor-a; C-C motif chemokine ligand 2, C-C motif chemokine receptor 5, C-reactive protein (CRP), intercellular adhesion molecule 1, transforming growth factor ß1, E-Selectin, selenoprotein S, cluster determinant 14, histone deacetylase 9 [HDAC9]). We constructed an extended gene score (EGS) as the sum of all individual risk alleles and analysed its effect on stroke, just as its association and interaction with cardiovascular risk factors and infectious scores (IgG antibodies against 5 respectively IgA antibodies against 4 microbial antigens). RESULTS: Cases were less likely to carry the minor allele of IL10 rs1800872 and more likely to carry the HDAC9 allele rs11984041 and the pro-inflammatory haplotype of CRP, although the latter was not statistically significant in our study. Overall, cases tended to have more pro-inflammatory alleles and haplotypes than controls (mean ± SD 13.25 ± 2.25 and 13.04 ± 2.41, respectively). However, the EGS only slightly and not significantly increased the risk of stroke (OR 1.04, 95% CI 0.99-1.09). Its effect was neither associated with included risk factors nor with IgA and IgG infectious scores, and we found no significant interaction effects. CONCLUSION: A more pro-inflammatory genetic profile might increase stroke risk to some extent. This potential effect is most likely independent of established cardiovascular risk factors and the infectious burden of an individual.

Quantitative Lesion Water Uptake in Acute Stroke Computed Tomography Is a Predictor of Malignant Infarction.

Background and Purpose- Early selection of patients with acute middle cerebral artery infarction at risk for malignant edema is critical to initiate timely decompressive surgery. Net water uptake (NWU) per brain volume is a quantitative imaging biomarker of space-occupying ischemic edema which can be measured in computed tomography. We hypothesize that NWU in early infarct lesions can predict development of malignant edema. The aim was to compare NWU in acute brain infarct against other common predictors of malignant edema. Methods- After consecutive screening of single-center registry data, 153 patients with acute proximal middle cerebral artery occlusion fulfilled the inclusion criteria. A total of 29 (18.2%) patients developed malignant edema defined as end point in follow-up imaging leading to decompressive surgery and death as a direct implication of mass effect. Early infarct lesion volume and NWU were quantified in multimodal admission computed tomography; time from symptom onset to admission imaging was recorded. Results- Mean time from onset to admission imaging was equivalent between patients with and without malignant infarcts (mean±SD: 3.3±1.4 hours and 3.3±1.7 hours, respectively). Edematous tissue expansion by NWU within infarct lesions occurred across all patients in this cohort (NWU: 9.1%±6.8%; median, 7.9%; interquartile range, 8.8%; range, 0.1%-35.6%); 7.0% (±5.2) in nonmalignant and 18.0% (±5.7) in malignant infarcts. Based on univariate receiver operating characteristic curve analysis, NWU >12.7% or an edema rate >3.7% NWU/h identified malignant infarcts with high discriminative power (area under curve, 0.93±0.02). In multivariate binary logistic regression, the probability of malignant infarct was significantly associated with early infarct volume and NWU. Conclusions- Computed tomography-based quantitative NWU in early infarct lesions is an important surrogate marker for developing malignant edema. Besides volume of early infarct, the measurements of lesion water uptake may further support identifying patients at risk for malignant infarction.

Association of gadolinium-enhanced magnetic resonance imaging with hepatic fibrosis and inflammation in primary sclerosing cholangitis.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI) parameters T2 signal, contrast enhancement (CE), and relative liver enhancement (RLE) of extracellular gadolinium-based contrast agent (GBCA)-enhanced MRI as a marker for hepatic fibrosis and inflammation in patients with primary sclerosing cholangitis (PSC). METHODS: 3.0-Tesla MRI scans and liver biopsies of 40 patients (41.2 ± 17.1 years) were retrospectively reviewed. Biopsies were obtained within a mean time of 54 ± 55 days to MRI scans and specimens were categorized according to Ishak modified hepatic activity index (mHAI) and Scheuer staging of fibrosis. T2 signal (N = 40), CE alterations (N = 29), and RLE (N = 29) were assessed by two raters. Mixed-effects regression models were applied to estimate the association between histopathology and MRI parameters. RESULTS: No significant association was observed between T2 signal or CE alterations with stages of fibrosis or mHAI grading. Regression models revealed significant positive associations of portal venous phase RLE with mHAI grade ≥ 7 points [ß = 25.5; 95% CI (2.53; 48.62); p = 0.04] and delayed phase RLE with stages of fibrosis [stage 2: ß = 35.13; 95% CI (11.35; 58.87); p = 0.007; stage 3/4: ß = 69.24; 95% CI (45.77; 92.75); p < 0.001]. The optimal cut-off value of 66.6% delayed phase RLE distinguished fibrosis stages 0-2 from 3-4 with a sensitivity of 0.833 and specificity of 0.972. Inter-rater reliability (IRR) for quantification of RLE was 'excellent' (r = 0.90-0.98). IRR was 'substantial' for detection of T2 signal in the right liver lobe (RL) (Kappa = 0.77) and 'almost perfect' for T2 signal of the left liver lobe (LL) and CE of both lobes (Kappa = 0.87-1.0). CONCLUSION: The simple and reproducible method of RLE quantification on standard extracellular GBCA-enhanced MRI may provide a correlate measure of advanced stages of hepatic fibrosis and potentially also inflammation in PSC patients, if validated in larger cohorts.

Estimating lung cancer mortality attributable to second hand smoke exposure in Germany.

OBJECTIVES: Public health measures such as nonsmoker protection laws affect smoking prevalence and consequently the number of lung cancer deaths attributable to second hand smoke (SHS). In Germany, a risk assessment of SHS has been performed in 1994 only, and therefore, a reassessment is of interest. METHODS: Based on current knowledge on the relative risk of lung cancer from SHS, SHS prevalence, lung cancer deaths in Germany, and two approaches to estimate the number of never smokers among lung cancer deaths, we estimated the current number of deaths attributable to SHS among never smokers in Germany. RESULTS: Based on a relative risk of 1.21 (95% CI 1.14-1.28), recent prevalence of SHS of 39.5% for men and 23.5% for women, the attributable risks are 7.66 and 4.70%, respectively. Out of about 47,000 lung cancer deaths per year, the estimated number of never smokers is about 6000, out of which we estimated 167 being attributable to SHS. CONCLUSIONS: Despite an aging population, the number of deaths from lung cancer attributable to SHS decreased considerably. This positive trend should be strengthened by further public health measures.

Contribution of Established Stroke Risk Factors to the Burden of Stroke in Young Adults.

BACKGROUND AND PURPOSE: As stroke in young adults is assumed to have different etiologies and risk factors than in older populations, the aim of this study was to examine the contribution of established potentially modifiable cardiovascular risk factors to the burden of stroke in young adults. METHODS: A German nationwide case-control study based on patients enrolled in the SIFAP1 study (Stroke In Young Fabry Patients) 2007 to 2010 and controls from the population-based GEDA study (German Health Update) 2009 to 2010 was performed. Cases were 2125 consecutive patients aged 18 to 55 years with acute first-ever stroke from 26 clinical stroke centers; controls (age- and sex-matched, n=8500, without previous stroke) were from a nationwide community sample. Adjusted population-attributable risks of 8 risk factors (hypertension, hyperlipidemia, diabetes mellitus, coronary heart disease, smoking, heavy episodic alcohol consumption, low physical activity, and obesity) and their combinations for all stroke, ischemic stroke, and primary intracerebral hemorrhage were calculated. RESULTS: Low physical activity and hypertension were the most important risk factors, accounting for 59.7% (95% confidence interval, 56.3-63.2) and 27.1% (95% confidence interval, 23.6-30.6) of all strokes, respectively. All 8 risk factors combined explained 78.9% (95% confidence interval, 76.3-81.4) of all strokes. Population-attributable risks of all risk factors were similar for all ischemic stroke subtypes. Population-attributable risks of most risk factors were higher in older age groups and in men. CONCLUSIONS: Modifiable risk factors previously established in older populations also account for a large part of stroke in younger adults, with 4 risk factors explaining almost 80% of stroke risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00414583.