Wernich †

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Basedow'sche Krankheit und Schilddrüse 1 )

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A novel pathogenic CACNA1A variant causing episodic ataxia type 2 (EA2) spectrum phenotype in four family members and a novel combined therapy

Objective!#!The safety and efficacy of surgical microvascular decompression (MVD) in elderly patients with trigeminal neuralgia (TN) is controversially discussed in the literature. A widespread reluctance to expose this cohort to major intracranial surgery persists. Our aim was to compare the efficacy and safety between older and younger patients with TN.!##!Methods!#!In this cross-sectional study, 139 MVD procedures (103 patients < 70 and 36 patients ≥ 70) were included. Surgical fitness was assessed by the American Society of Anesthesiology (ASA) grade. The pain-free interval was evaluated using Kaplan-Meier analysis only in patients with a recent follow-up visit. Independent risk factors for recurrence in patients with a minimum 12-month follow-up were determined.!##!Results!#!Patients ≥ 70 showed a significantly higher number of comorbidities. Pain intensity, affection of trigeminal branches and symptom duration was similar between groups. No significant difference in treatment associated complications and permanent neurological deficits was shown. There was no treatment-related mortality. A tendency towards a lower recurrence rate in patients < 70 did not reach statistical significance (17.6% vs. 28.6%, P = 0.274). Pain-free interval was not different between both cohorts (78.7 vs. 73.5 months, P = 0.391).!##!Conclusion!#!Despite a higher prevalence of comorbidities in elderly patients, complication rates and neurological deficits after MVD were comparable to younger patients. Rates of immediate and long-term pain relief compared favorably to previous studies and were similar between elderly and younger patients. These data endorse MVD as a safe and effective first-line surgical procedure for elderly patients with TN and neurovascular conflict on MRI

Lena Delta hydrology and geochemistry: long-term hydrological data and recent field observations

The Lena River forms one of the largest deltas in the Arctic. We compare two sets of data to reveal new insights into the hydrological, hydrochemical, and geochemical processes within the delta: (i) long-term hydrometric observations at the Khabarova station at the head of the delta from 1951 to 2005; (ii) field hydrological and geochemical observations carried out within the delta since 2002. Periods with differing relative discharge and intensity of fluvial processes were identified from the long-term record of water and sediment discharge. Ice events during spring melt (high water) reconfigured branch channels and probably influenced sediment transport within the delta. Based on summer field measurements during 2005–2012 of discharge and sediment fluxes along main delta channels, both are increased between the apex and the front of the delta. This increase is to a great extent connected with an additional influx of water from tributaries, as well as an increase of suspended and dissolved material released from the ice complex. Summer concentrations of major ion and biogenic substances along the delta branches are partly explained by water sources within the delta, such as thawing ice complex waters, small Lena River branches and estuarine areas

Comparison of health behaviours between cancer survivors and the general population:a cross-sectional analysis of the Lifelines cohort

Purpose: To compare the differences in lifestyle behaviours between cancer survivors (CSs) and cancer-free participants in a large and representative population-based cohort. Methods: We included 115,257 adults from the Lifelines cohort. Cancer status was self-reported, and health behaviours were measured (e.g. body mass index [BMI]) or assessed by questionnaire (e.g. physical activity, smoking, alcohol consumption, sedentary behaviour and diet). The data were then categorised for logistic regression analysis, stratified and adjusted by sex and age (< 55 vs ≥ 55 years). Results: CSs (5473; 4.7%) were diagnosed 9 ± 8.5 years before data collection, were older (mean age 55.4 vs 44.4 years) and more often female (66.6% vs 33.4%) than the cancer-free participants. They were also more likely to be physically active and to have a better diet, and also less likely to be alcohol drinkers; but, were more likely to have a higher BMI, be former smokers and to be sedentary. After adjustment for sex and age, however, BMI was more likely to be normal, physical activity was more likely to be higher and smoking to be prevalent in CSs. Current smoking was also significantly higher among females and those aged < 55 years who were CSs than for those with no history of cancer. Conclusions: In this population-based cohort, CSs have health behaviour comparable to those without a cancer diagnosis. Implications for cancer survivors: Smoking cessation strategies should target all CSs, but efforts could yield greatest benefit if they target females and those younger than 55 years

Higher Programmatic Volume in Neonatal Heart Surgery Is Associated With Lower Early Mortality

BACKGROUND: The early results of congenital heart surgery in neonates remain a challenge. We sought to determine the nature of the association between annual center volume of neonatal cardiac surgery and operative mortality using a multicenter cohort. METHODS: The dataset consists of 27,556 neonatal procedures performed between 1999 and 2015 in 90 centers participating in the European Congenital Heart Surgeons Association database. Centers with mean annual volume load of six or more that submitted data for at least 3 consecutive years were included. World Bank annual gross national index per capita was utilized as an indicator of temporal national affluence. Multilevel logistic regression was used to create a model including the significant risk factors and to calculate odds ratios for operative mortality. Iterative modeling of the dataset incrementally excluding centers with lower annual caseload was used to identify the relationship between annual volume and mortality. RESULTS: In the model thus calculated including The Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) mortality score, operative weight and age, noncardiac genetic anomalies, and annual volume of operations were independent risk factors for operative mortality in the analysis of the entire cohort. In the model containing these variables, annual gross national index and year of surgery were not significantly associated with mortality. In the iterative process, annual volume ceased to be a risk factor when units operating on fewer than 60 neonates annually were excluded. CONCLUSIONS: In neonatal congenital heart surgery, the risk of operative death decreased with the increase of volume load. The cutoff point in this cohort was a mean annual volume of 60 neonatal operations per year.info:eu-repo/semantics/publishedVersio

The lidocaine metabolite N-ethylglycine has antinociceptive effects in experimental inflammatory and neuropathic pain

Glycine transporter 1 (GlyT1) plays a crucial role in regulating extracellular glycine concentrations and might thereby constitute a new drug target for the modulation of glycinergic inhibition in pain signaling. Consistently with this view, inhibition of GlyT1 has been found to induce antinociceptive effects in various animal pain models. We have shown previously that the lidocaine metabolite N-ethylglycine (EG) reduces GlyT1-dependent glycine uptake by functioning as an artificial substrate for this transporter. Here we show that EG is specific for GlyT1 and that in rodent models of inflammatory and neuropathic pain, systemic treatment with EG results in an efficient amelioration of hyperalgesia and allodynia without affecting acute pain. There was no effect on motor coordination or the development of inflammatory edema. No adverse neurologic effects were observed following repeated high-dose application of EG. EG concentrations both, in blood and spinal fluid, correlated with an increase of glycine concentration in spinal fluid. The time courses of the EG and glycine concentrations corresponded well with the antinociceptive effect. Additionally, we found that EG reduced the increase in neuronal firing of wide-dynamic-range neurons caused by inflammatory pain induction. These findings suggest that systemically applied lidocaine exerts antihyperalgesic effects via its metabolite EG in vivo, by enhancing spinal inhibition of pain processing through GlyT1 modulation and subsequent increase of glycine concentrations at glycinergic inhibitory synapses. EG and other substrates of GlyT1, therefore, may be a useful therapeutic agent in chronic pain states involving spinal disinhibition

Vascular aging in long-term survivors of testicular cancer more than 20 years after treatment with cisplatin-based chemotherapy

Background: Late effects of cisplatin-based chemotherapy in testicular cancer survivors (TCS) include cardiovascular morbidity, but little data is available beyond 20 years. The objective was to assess vascular damage in very long-term TCS. Methods: TCS (treated with chemotherapy or orchiectomy only) and age-matched healthy controls were invited. Study assessment included vascular stiffness with ultrasound measurement of carotid-femoral pulse wave velocity (cf-PWV). Results: We included 127 TCS consisting of a chemotherapy group (70 patients) and an orchiectomy group (57 patients) along with 70 controls. Median follow-up was 28 years (range: 20–42). The cf-PWV (m/s) was higher in TCS than in controls (geometrical mean 8.05 (SD 1.23) vs. 7.60 (SD 1.21), p = 0.04). The cf-PWV was higher in the chemotherapy group than in the orchiectomy group (geometrical mean 8.39 (SD 1.22) vs. 7.61 (SD 1.21), p < 0.01). In the chemotherapy group cf-PWV increased more rapidly as a function of age compared to controls (regression coefficient b 7.59 × 10−3 vs. 4.04 × 10−3; p = 0.03). Conclusion: Very long-term TCS treated with cisplatin-based chemotherapy show increased vascular damage compatible with “accelerated vascular aging” and continue to be at risk for cardiovascular morbidity, thus supporting the need for intensive cardiovascular risk management. Clinical trial registration: The clinical trial registration number is NCT02572934