Inpatient treatment of patients with acute idiopathic peripheral facial palsy: A population-based healthcare research study.

OBJECTIVES: To determine the inpatient management for patients with acute idiopathic facial palsy (IFP) in Thuringia, Germany. DESIGN: Population-based study. SETTING: All inpatients with IFP in all hospitals with departments of otolaryngology and neurology in 2012, in the German federal state, Thuringia. MAIN OUTCOME MEASURES: Patients' characteristics and treatment were compared between departments, and the probability of recovery was tested. RESULTS: A total of 291 patients were mainly treated in departments of otolaryngology (55%) and neurology (36%). Corticosteroid treatment was the predominant therapy (84.5%). The probability to receive a facial nerve grading (odds ratio [OR=12.939; 95% confidence interval [CI]=3.599 to 46.516), gustatory testing (OR=6.878; CI=1.064 to 44.474) and audiometry (OR=32.505; CI=1.485 to 711.257) was significantly higher in otolaryngology departments, but lower for cranial CT (OR=0.192; CI=0.061 to 0.602), cerebrospinal fluid examination (OR=0.024; CI=0.006 to 0.102). A total of 131 patients (45%) showed a recovery to House-Brackmann grade≤II. A pathological stapedial reflex test (Hazard ratio [HR]=0.416; CI=0.180 to 0.959) was the only independent diagnostic predictor of worse outcome. Prednisolone dose >500 mg (HR=0.579; CI 0.400 to 0.838) and no adjuvant physiotherapy (HR=0.568; CI=0.407 to 0.794) were treatment-related predictors of worse outcome. CONCLUSIONS: Inpatient treatment of IFP seems to be highly variable in daily practice, partly depending on the treating discipline and despite the availability of evidence-based guidelines. The population-based recovery rate was worse than reported in clinical trials.

Prediction of activity-related energy expenditure using accelerometer-derived physical activity under free-living conditions: a systematic review.

BACKGROUND/OBJECTIVES: Activity-related energy expenditure (AEE) might be an important factor in the etiology of chronic diseases. However, measurement of free-living AEE is usually not feasible in large-scale epidemiological studies but instead has traditionally been estimated based on self-reported physical activity. Recently, accelerometry has been proposed for objective assessment of physical activity, but it is unclear to what extent this methods explains the variance in AEE. SUBJECTS/METHODS: We conducted a systematic review searching MEDLINE database (until 2014) on studies that estimated AEE based on accelerometry-assessed physical activity in adults under free-living conditions (using doubly labeled water method). Extracted study characteristics were sample size, accelerometer (type (uniaxial, triaxial), metrics (for example, activity counts, steps, acceleration), recording period, body position, wear time), explained variance of AEE (R(2)) and number of additional predictors. The relation of univariate and multivariate R(2) with study characteristics was analyzed using nonparametric tests. RESULTS: Nineteen articles were identified. Examination of various accelerometers or subpopulations in one article was treated separately, resulting in 28 studies. Sample sizes ranged from 10 to 149. In most studies the accelerometer was triaxial, worn at the trunk, during waking hours and reported activity counts as output metric. Recording periods ranged from 5 to 15 days. The variance of AEE explained by accelerometer-assessed physical activity ranged from 4 to 80% (median crude R(2)=26%). Sample size was inversely related to the explained variance. Inclusion of 1 to 3 other predictors in addition to accelerometer output significantly increased the explained variance to a range of 12.5-86% (median total R(2)=41%). The increase did not depend on the number of added predictors. CONCLUSIONS: We conclude that there is large heterogeneity across studies in the explained variance of AEE when estimated based on accelerometry. Thus, data on predicted AEE based on accelerometry-assessed physical activity need to be interpreted cautiously.

[Indications and outcome of ventilated patients treated in a neurological intensive care unit]. / Indikationen und Outcome beatmeter Patienten einer neurologischen Intensivstation.

OBJECTIVE: This study characterized artificially ventilated patients in a neurological intensive care unit (NICU) between 2006-2008 in a purely neurological clinic and a so-called stand-alone situation. In addition the long-term prognoses as well as the quality of life of surviving patients were investigated. METHODS: All ventilated patients from October 2006 to December 2008 were enrolled in this descriptive, retrospective study. The duration of stay in intensive care was analyzed and the current quality of life was prospectively assessed based on the patient records. Final diagnoses, duration of intensive care unit and ventilation as well as the highest score in SAPS II (simplified acute physiology score) and complications during hospitalization were determined. The patients were divided into groups based on the diagnoses as vascular, inflammatory, neurodegenerative, hereditary, epileptogenic and others. Additionally patients were contacted and asked to respond by completing questionnaires on the Barthel index (BI) and the modified Rankin scale (mRS). RESULTS: During the study period a total of 512 patients were treated in the NICU of whom 201 required artificial respiration. Cerebrovascular diseases were the main reason for therapy in the NICU in 96 out of 201 cases (47.8%), followed by inflammatory diseases in 46 (22.8%) and epileptogenic diseases in 26 patients (13%). The median duration of artificial respiration was 9 days with a mean treatment duration of 16 days (range 1-57 days). Of the patients 31 (15.4%) died in the NICU and an additional 32 patients (18.8%) died within a median of 2 months after discharge. Outcome data were available from 67 out of 170 sent questionnaires and rehabilitation reports of 86 patients, which enabled the outcome of 121 surviving patients to be analyzed (71.2%). Of these 42.2% showed no or mild impairment in everyday life. However, the remaining 38% had severe impairments according to the BI. The evaluation of the mRS showed that 49.6% of the patients still had severe symptoms. CONCLUSIONS: More than one third of the patients treated in the NICU required artificial ventilation with an emphasis on cerebrovascular diseases, which illustrates the overlap between stroke unit and NICU care. Despite a lengthy duration of ventilation and a long stay in the intensive care unit more than one third of surviving patients showed no or only mild impairment. However, an additional third suffered from severe disability up to nursing care dependency. The study data differ little from the few publications in this field despite the stand alone situation of the NICU. The case mix index per day averaged around 0.3 and underlines the economic importance with respect to other forms of neurological treatment.

The antidepressant rolipram suppresses cytokine production and prevents autoimmune encephalomyelitis.

In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) the cytokines tumour necrosis factor-alpha (TNF), lymphotoxin-alpha (LT), and interferon-gamma (IFN-gamma) are of central pathogenetic importance. A therapy capable of stopping neurological deterioration in MS patients is not yet available. Here, we report that rolipram, a selective type IV phosphodiesterase inhibitor, stereospecifically suppresses the production of TNF/LT and less strongly also IFN-gamma in human and rat auto-reactive T cells. Moreover, we show that rolipram is an effective treatment for EAE. Rolipram has extensively been studied in humans for the treatment of depression, but has not yet been marketed. The data presented here identify rolipram as potential therapy for multiple sclerosis and provoke the immediate initiation of clinical trials.

Meat consumption and risk of type 2 diabetes: the Multiethnic Cohort.

OBJECTIVE: To examine the association of meat consumption with diabetes risk in the Hawaii component of the Multiethnic Cohort and to assess effect modification by ethnicity. DESIGN: A prospective cohort study. Baseline information on diet and lifestyle was assessed by questionnaire. The cohort was followed up for incident cases of diabetes, which were identified through self-reports, medication questionnaires, or health plan linkages. Cox regression was used to calculate hazard ratios (HR) and 95% confidence intervals for diabetes associated with quintile of meat consumption. SETTING: Hawaii, USA. SUBJECTS: A total of 29,759 Caucasian, 35,244 Japanese-American and 10,509 Native Hawaiian men and women, aged 45-75 years at baseline. RESULTS: During a mean follow-up time of 14 years, 8587 incident diabetes cases were identified. Intake of red meat was positively associated with diabetes risk in men (fifth v. first quintile: HR=1.43; 95% CI 1.29, 1.59) and women (fifth v. first quintile: HR=1.30; 95% CI 1.17, 1.45) in adjusted models. The respective HR for processed red meat intake were 1.57 (95% CI 1.42, 1.75) and 1.45 (95% CI 1.30, 1.62). The association for processed poultry was weaker than for processed red meat, and fresh poultry intake was not associated with diabetes risk. For men only, we observed significant interactions of ethnicity with the red and processed red meat associations, with Caucasians experiencing slightly higher risks than Japanese-Americans. CONCLUSIONS: Our findings support the growing evidence that red and processed meat intake increase risk for diabetes irrespective of ethnicity and level of BMI.

[About the cultural history of dog-keeping in the early modern age: A (re)reading of rabies treatises.]. / Zur Kulturgeschichte der Hundehaltung in der Vormoderne: Eine (Re)Lektüre von Tollwut-Traktaten.

Rabies treatises of the 18th and 19th century are being researched in regard to their significance of the keeping of pets, which started to establish itself at the beginning of the 17th century. In doing so it is clearly recognizable that this keeping of pets had become a constant element of the civil urban life. The treatises also show that the physicians declined the keeping of dogs out of pure pleasure.

[Severe tick-borne encephalomyelitis with lack of cerebrospinal fluid pleocytosis]. / Schwere Frühsommer-Meningo-Enzephalomyelitis ohne Liquor-Pleozytose.

Tick borne encephalitis (TBE) is an important viral encephalitis in central and eastern Europe. Cerebrospinal fluid (CSF) pleocytosis has been described in all published patients so far. This may be due to selection bias, however, as CSF pleocytosis is often used as a case definition parameter. The frequency of TBE without CSF pleocytosis is unknown. We report two cases who developed severe TBE without CSF pleocytosis. A normal CSF cell count should therefore not discourage from the differential diagnosis of TBE and deter from serological testing in patients with a clinical constellation suggesting TBE.

Low-dose chemotherapy in combination with COX-2 inhibitors and PPAR-gamma agonists in recurrent high-grade gliomas - a phase II study.

OBJECTIVES: Combined treatment approaches targeting tumor as well as other cells contributing to tumor progression may control chemorefractory malignancies. METHODS: A phase II trial was initiated to analyze the activity of continuously administered pioglitazone and rofecoxib combined with low-dose chemotherapy (capecitabine or temozolomide) in patients with high-grade gliomas (glioblastoma or anaplastic glioma). RESULTS: Fourteen patients were evaluable for response and toxicity. Major side effects were palmoplantar erythema, edema and motor neuropathy grade 3. Disease stabilizations lasting longer than 3 months were noted in 4 of 14 patients (29%). Clinical responses did not correspond to immunohistochemical staining for cyclooxygenase 2, peroxisome proliferator-activated receptor-gamma and CD31. DISCUSSION: The study demonstrates that this novel regimen is moderately active and well tolerated in patients with high-grade gliomas. As a comparably small proportion of patients responded, the regimen might only be suitable for a subset of highly selected patients.

Calcified neurocysticercosis lesions trigger symptomatic inflammation during antiparasitic therapy.

We report a patient with neurocysticercosis who developed numerous cerebral edematous lesions while undergoing cysticidal therapy. These lesions outnumbered viable cystic lesions seen before therapy. Most new lesions were subsequently found to be associated with former calcifications not seen on initial MR imaging. Calcified neurocysticercosis lesions can trigger inflammatory reactions during therapy, and the number and location of calcified neurocysticercosis lesions may influence treatment decisions.

Autonomic involvement in tick-borne encephalitis (TBE): report of five cases.

BACKGROUND: Tick-borne encephalitis (TBE) is a viral infection of the CNS with significant acute and long-term morbidity. Dysfunction of the autonomic nervous system may be a potentially harmful complication of TBE. MATERIAL AND METHODS: In a retrospective case series, 5 patients with acute TBE were evaluated for clinical signs of autonomic dysfunction and subject to autonomic testing. Heart rate variability (HRV) with 6 per minute deep breathing was performed between day 9 to 31 after onset of meningitis. Follow-up data were available in three cases. RESULTS: All patients showed clinical signs of autonomic dysfunction, including upper and lower gastrointestinal tract symptoms, orthostatic hypotension, and urinary retention. A reduced HRV was observed in 4 patients, with sustained sinus tachycardia in 2 of them. The minimum of the HRV was reached 9 to 20 days after onset of meningitis. In one patient, normalization of the HRV occurred within 3 months. CONCLUSION: Acute TBE can be associated with autonomic dysfunction including reduced HRV and tachycardia. Prospective studies are needed to analyze the incidence of autonomic dysfunction in TBE, and to clarify which patients have the highest risk for autonomic failure.

Targeting fibroblast growth factor-inducible-14 signaling protects from chronic relapsing experimental autoimmune encephalomyelitis.

The TNF-related weak inducer of apoptosis (TWEAK) is a TNF family member mediating proinflammatory effects by its receptor fibroblast growth factor-inducible-14 (Fn14). We studied the role of TWEAK/Fn14 in experimental autoimmune encephalomyelitis (EAE) by protein vaccination with TWEAK and Fn14 and recombinant TWEAK-DNA, respectively. TWEAK-DNA vaccination worsened the clinical course of EAE and increased central nervous system (CNS) inflammation. TWEAK increased the secretion of CCL2 [monocyte chemotactic protein-1 (MCP-1)] by CNS endothelial cells and astrocytes in vitro, suggesting CCL2 as a critical mediator of TWEAKs proinflammatory effects. Vaccination with the extracellular domain of TWEAK or with Fn14 resulted in the induction of specific inhibitory antibodies and an amelioration of EAE signs in two different models in rats and mice. Spinal cord inflammatory infiltrates were significantly diminished. Purified IgG from TWEAK- or Fn14-vaccinated rats prevented TWEAK-induced production of CCL2 by endothelial cells. Blocking Fn14 signaling represents a novel approach with potential for the treatment of CNS autoimmunity.

Adult medulloblastoma: prognostic factors and response to therapy at diagnosis and at relapse.

Adult medulloblastoma is a rare tumor with few retrospective studies published so far. The role of adjuvant chemotherapy or chemotherapy at relapse is unclear. This study reports therapy and outcome in all adult (>or=16 years old) medulloblastoma (n=34) and supratentorial primitive neuroectodermal tumor (PNET) patients (n=2) treated in 2 neuro-oncological centers between 1976 and 2002. The median age was 24.5 years (range 16-76). After resection, 16 patients were treated with craniospinal radiotherapy alone, 20 patients also received adjuvant chemotherapy (8 vincristine, CCNU, cisplatin; 7 methotrexate alone or methotrexate/vincristine-based polychemotherapy; 5 other protocols). Median survival in the whole cohort was 126 months (2+ - 200+months). Five-year and 10-year survival rates were 79 % and 56%. Adjuvant chemotherapy was associated with a non-significant trend to prolonged survival (relative risk (RR) 1.89; p=0.068). The median progression-free survival (PFS) after primary therapy was 83 months. At relapse, 10 of 12 evaluable patients achieved a complete response upon second-line therapy. The median survival times from first (n=17) and second relapse (n=9) were 21 months (0-67+ months; 5/17 without second relapse) and 20 months (1-29 months). Cox regression analysis revealed the infiltration of the floor of the 4(th) ventricle at diagnosis as the only therapy-independent prognostic factor (RR 0.48; p=0.03). In conclusion, adjuvant chemotherapy may prolong survival in adult medulloblastoma patients. Moreover, second-line therapy may be beneficial for these patients. As in pediatric medulloblastoma patients, primary infiltration of the floor of the 4(th) ventricle indicates a poor prognosis.

Dipeptidyl peptidase IV in inflammatory CNS disease.

Current pathogenic concepts of inflammatory demyelinating disorders such as multiple sclerosis (MS) are based on the hypothesis that a T cell-mediated autoimmune response is involved in the disease process. One of the primary goals in the in the development of immunotherapies for autoimmune diseases has been to achieve inactivation of disease-inducing lymphocytes either by direct inhibition or suppression through regulatory cells and/or cytokines. The CD26 antigen is identical with the cell surface ectopeptidase dipeptidyl peptidase IV (DP IV, EC 3.4.14.5) which is involved in regulating T cell activation and growth. Activated T cells, including those specific for myelin antigens, express high levels of CD26/DP IV. In vitro, reversible DP IV inhibitors suppress T cell proliferation and pro-inflammatory cytokine production in response to myelin antigens. Further studies will evaluate the role of DP IV inhibition in T cell-mediated inflammatory disease of the central nervous system.

Dipeptidyl peptidase IV (CD26): role in T cell activation and autoimmune disease.

The ectoenzyme dipeptidyl peptidase IV (DP IV; EC 3.4.14.5; CD26) has been shown to play a crucial role in T cell activation. In the present study, we show by flow cytometry and by enzymatic DP IV assay that myelin basic protein (MBP)-specific, CD4+ T cell clones (TCC) derived from patients with multiple sclerosis (MS) express high levels of DP IV/CD26. The enzymatic activity of resting TCC was found to be three to fourfold higher than on resting peripheral blood T cells and close to that of T cells 48 hours after PHA stimulation. The DP IV inhibitors Lys[Z(NO2)]-thiazolidide and Lys[Z(NO2)]-pyrrolidide suppress in a dose-dependent manner DNA synthesis and IFN-gamma, IL-4, and TNF-alpha production of the antigen-stimulated TCC. These data suggest that CD26 plays a role in regulating activation of autoreactive TCC. Further in vivo investigations will clarify, whether the inhibition of the enzymatic activity of DP IV could be a useful tool for therapeutic interventions in MS and/or other autoimmune diseases.

Development and evaluation of a short 24-h food list as part of a blended dietary assessment strategy in large-scale cohort studies.

BACKGROUND/OBJECTIVES: The validity of dietary assessment in large-scale cohort studies has been questioned. Combining data sources for the estimation of usual intake in a blended approach may enhance the validity of dietary measurement. Our objective was to develop a web-based 24-h food list for Germany to identify foods consumed during the previous 24 h and to evaluate the performance of the new questionnaire in a feasibility study. SUBJECTS/METHODS: Available data from the German National Nutrition Survey II were used to develop a finite list of food items. A total of 508 individuals were invited to fill in the 24-h food list via the Internet up to three times during a 3-6-month time period. In addition, participants were asked to evaluate the questionnaire using a brief online evaluation form. RESULTS: In total, 246 food items were identified for the 24-h food list, reflecting >75% variation in intake of 27 nutrients and four major food groups. Among the individuals invited, 64% participated in the feasibility study. Of these, 100%, 85% and 68% of participants completed the 24-h food list one, two or three times, respectively. The average time needed to complete the questionnaire was 9 min, and its acceptability by participants was rated as high. CONCLUSIONS: The 24-h food list represents a promising new dietary assessment tool that can be used as part of a blended approach combining multiple data sources for valid estimation of usual dietary intake in large-scale cohort studies.

Urinary estrogen metabolites in two soy trials with premenopausal women.

BACKGROUND: Soy consumption may protect against breast cancer through modification of estrogen metabolism. OBJECTIVES: We examined the effect of soy foods on urinary estrogens and the 2-hydroxy (OH)/16α-OH estrone (E(1)) ratio in two dietary interventions with premenopausal women. SUBJECTS/METHODS: The Breast, Estrogens, And Nutrition (BEAN1) study was a 2-year randomized trial and BEAN2 a 13-month randomized crossover study. In both interventions, study participants consumed a high-soy diet with 2 soy food servings/day and a low-soy diet with <3 servings of soy/week. Urine samples were collected at baseline and at the end of the diet periods, analyzed for nine estrogen metabolites by liquid chromatography mass spectrometry, and adjusted for creatinine levels. For BEAN1, two samples for 188 participants and for BEAN2, three samples for 79 women were analyzed. We applied mixed-effects regression models with log-transformed values of estrogen metabolites and soy intake as the exposure variable. RESULTS: In BEAN1, no effect of the high-soy diet on individual estrogen metabolites or hydroxylation pathways was observed. The median 2-OH/16α-OHE(1) ratio decreased non-significantly in the intervention group from 6.2 to 5.2 as compared with 6.8 and 7.2 in the control group (P=0.63). In BEAN2, only 4-OHE(1) was significantly lower after the high-soy diet. Interaction terms of the high-soy diet with equol producer status, ethnicity and weight status revealed no significant effect modification. CONCLUSIONS: Contrary to our hypothesis and some previous reports, the results from two well-controlled dietary interventions do not support an effect of a high-soy diet on a panel of urinary estrogen metabolites and the 2-OH/16α-OHE(1) ratio.

The association of education with long-term weight change in the EPIC-PANACEA cohort.

BACKGROUND/OBJECTIVES: Cross-sectionally, educational attainment is strongly associated with the prevalence of obesity, but this association is less clear for weight change during adult life. The objective of this study is to examine the association between educational attainment and weight change during adult life in the European Prospective Investigation into Cancer and Nutrition (EPIC). SUBJECTS/METHODS: EPIC is a cohort study with 361,467 participants and up to 10 years of follow-up. Educational attainment was categorized according to the highest obtained school level (primary school or less, vocational secondary training, other secondary education and university). Multivariate mixed-effects linear regression models were used to study education in relation to weight at age 20 years (self-reported), to annual change in weight between age 20 years and measured weight at recruitment, and to annual change in weight during follow-up time. RESULTS: Higher educational attainment was associated with on average a lower body mass index (BMI) at age 20 years and a lower increase in weight up to recruitment (highest vs lowest educational attainment in men: -60 g per year (95% confidence interval (CI) -80; -40), women -110 g per year (95% CI -130; -80)). Although during follow-up after recruitment an increase in body weight was observed in all educational levels, gain was lowest in men and women with a university degree (high vs low education -120 g per year (95% CI -150; -90) and -70 g per year (95% CI -90; -60), respectively). CONCLUSIONS: Existing differences in BMI between higher and lower educated individuals at early adulthood became more pronounced during lifetime, which possibly impacts on obesity-related chronic disease risk in persons with lower educational attainment.

Soy consumption is not protective against diabetes in Hawaii: the Multiethnic Cohort.

Based on the hypothesis that soy consumption may improve glucose tolerance, we examined the association of soy intake with diabetes risk in the Hawaii component of the Multiethnic Cohort. Among 29 719 Caucasian, 35 141 Japanese American and 10 484 Native Hawaiian men and women, 8564 incident diabetes cases were identified during 14 years of follow-up. Cox regression was used to calculate hazard ratios while adjusting for known confounders with stratifications by sex, ethnicity and weight status. We observed no protective effect of soy food consumption on diabetes risk in this population, which has a wide range of soy intakes though lower than in Asian populations. Indeed, higher soy food intake was associated with a weakly elevated diabetes risk across ethnic groups; the higher risk was limited to overweight and obese individuals. The current findings do not support a protective effect of modest levels of soy food consumption against diabetes.

Ethnic differences in weight gain and diabetes risk: the Multiethnic Cohort Study.

AIM: To improve our understanding of excess body weight and risk for diabetes type 2, the study examined the influence of weight change in the Hawaii component, including 78,006 Caucasians, Japanese Americans and Native Hawaiians, of the Multiethnic Cohort Study. METHODS: Participants aged 58.5±9.2 years completed a questionnaire at cohort entry (Qx1), including weight at age 21, and a follow-up questionnaire 5 years later (Qx2). After 14 years of follow-up, 8892 incident diabetes cases were identified through self-reports or linkups with the major health plans in Hawaii. Cox regression analysis was applied, stratified by age and adjusted for confounders, to estimate hazard ratios (HRs). RESULTS: The mean weight gain from age 21 to Qx1 was 10.5±11.0 kg and, between Qx1 and Qx2, 0.8±5.6 kg. Diabetes risk showed a significant dose-response relationship with weight gain from age 21 (P<0.0001). The respective HRs for a weight gain of 5-10 kg and greater or equal to 25 kg were 1.8 (95% CI: 1.7-2.0) and 7.7 (95% CI: 7.1-8.4), while weight loss of greater than 5 kg significantly reduced diabetes risk (HR=0.7; 95% CI: 0.6-0.9). The interaction term of weight change since age 21 with ethnicity was also highly significant (P<0.0001). Compared with stable-weight Caucasians, the adverse effects of weight gain were more pronounced in those of Japanese and Native Hawaiian descent. Weight change between Qx1 and Qx2 conferred a smaller risk. CONCLUSION: These findings support the current public-health recommendations for weight control and particularly among ethnic groups at high risk for diabetes.