Screening and surveillance recommendations for central nervous system hemangioblastomas in pediatric patients with Von Hippel-Lindau disease.

PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients. METHODS: We performed a retrospective analysis on a pediatric cohort of 99 VHL patients consulted at our VHL center from 1992 to 2023. Clinical, surgical, genetic, and imaging data were collected and statistically analyzed. RESULTS: 42 patients (50% male) developed CNS hemangioblastomas, of whom 18 patients (56% male) underwent hemangioblastoma surgery (mean age at first surgery: 14.9 ± 1.9 years; range 10.2-17). The first asymptomatic patient was operated on at the age of 13.2 years due to tumor progress. Truncating VHL mutation carriers had a significantly higher manifestation rate (HR = 3.7, 95% CI: 1.9-7.4, p < 0.0001) and surgery rate (HR = 3.3, 95% CI: 1.2-8.9, p = 0.02) compared with missense mutation carriers. CONCLUSION: We recommend starting MRI imaging at the age of 12 years with examination intervals every (1-) 2 years depending on CNS involvement. Special attention should be paid to patients with truncating variants. Affected families should be educated regularly on potential tumor-associated symptoms to enable timely MRI imaging and eventually intervention, as CNS hemangioblastoma may develop before screening begins. GERMAN CLINICAL TRIALS REGISTER REGISTRATION NUMBER: DRKS00029553, date of registration 08/16/2022, retrospectively registered.

A qualitative study on the patient's narrative in the progression of chronic venous disease into a first venous leg ulcer: a series of events.

BACKGROUND: A venous leg ulcer (VLU) has a significant negative impact on quality of life. Prevention of a VLU is not yet imbedded in clinical practice because risk factors for developing a first VLU are not well known. OBJECTIVES: To explore further the progression of chronic venous disease (CVD) into a first VLU from the patient's perspective. METHODS: A qualitative study using semistructured interviews was conducted among male and female patients with a VLU. Patients from primary and secondary care, under and over 50 years of age, and with first and recurrent VLUs were included. The interviews were transcribed and analysed using a narrative approach to a thematic analysis. Transcripts were organized in chronological order and an iterative process was used to code the transcripts. RESULTS: Four key themes and the connections made between them emerged from the 11 narratives on the progression of CVD towards a first VLU: 'comorbidity', 'mobility', 'work and lifestyle' and 'acknowledgment of CVD'. Comorbidity was linked to reduced mobility and late acknowledgment of CVD. Comorbidity also affected work and lifestyle and vice versa. Work and lifestyle affected mobility and was linked to the acknowledgment of CVD. CONCLUSIONS: A reduction in mobility as a result of comorbidity and work and lifestyle occurred before the VLU developed. Patients did not recognize symptoms of CVD and did not acknowledge the chronicity of CVD. Healthcare professionals should be aware of reductions in mobility and the knowledge deficit in patients with CVD. What's already known about this topic? Not all patients with chronic venous disease (CVD) develop a venous leg ulcer (VLU). A patient's quality of life decreases significantly when a VLU develops. Risk factors for the development of a first VLU in patients with CVD are not well known, unlike risk factors for other chronic wounds like diabetic foot ulcer and pressure ulcers. What does this study add? The patient's narrative towards the development of a first VLU, a series of events. Insight into the events (comorbidity, mobility, work and lifestyle) that patients themselves link to the development of a VLU. Insight into the patients' acknowledgment of CVD in the progression of CVD towards a first VLU. What are the clinical implications of this work? More awareness is needed of CVD symptoms among patients and healthcare providers, as well as more awareness for prevention of a VLU in clinical practice. New insights (for further studies) are needed into the concept of mobility and the development of a VLU. Improved patient education and follow-up are needed for patients with CVD.

A scoping review on Chronic Venous Disease and the development of a Venous Leg Ulcer: The role of obesity and mobility.

OBJECTIVE: The risk factors obesity and reduced mobility are not well known in the development of a Venous Leg Ulcer (VLU). The aim of this scoping review is to explore the mechanisms by which obesity and reduced mobility contribute the development of a VLU in patients with Chronic Venous Disease (CVD). METHODS: For this scoping review a search was performed in May 2019 in the Cochrane Library and Pubmed to identify studies on the working mechanisms of obesity and mobility in developing a VLU. Hand searches were performed to find additional studies explaining the working mechanisms (indirectly related to the VLU). Two reviewers independently reviewed the abstracts and full-text articles. RESULTS: Twenty-eight studies met our eligibility criteria. Disturbed range of ankle motion and gait can lead to a reduced Calf Muscle Pump (CMP) function which leading to a venous outflow disorder. Increased abdominal pressure due to obesity can lead to a venous outflow obstruction and increased adipose tissue mass results in an increase in adipokine secretion. The venous outflow disorder, outflow obstruction and increased adipokine secretion can all lead to chronic systemic inflammation, increased endothelial permeability and hence microcirculatory dysfunction. This alone can result in a VLU. CONCLUSION: Obesity and reduced mobility can lead to a reduction of the CMP function, an increase in abdominal pressure and an increase in adipose tissue mass. This can simultaneously lead to haemodynamic changes in the macro- and microcirculation of the lower extremities and eventually in a VLU. In patients with obesity and reduced mobility the microcirculation alone can lead to skin changes and eventually a VLU. Therefore, early recognition of CVD symptoms in patients with obesity and reduced mobility is crucial to diagnose and treat CVD to prevent a VLU.

A systematic review on risk factors in developing a first-time Venous Leg Ulcer.

Venous Leg Ulcers (VLU) occur in about 1% of the Western population. A VLU takes 3-12 months to heal, it recurs often, and it has a negative impact on the quality of life. The risk factors for the development of a first VLU are not well-understood and prevention of a first VLU therefore remains underappreciated. The aim of this study was to identify risk factors for developing a first VLU in adults (aged > 18 years) by searching the literature. We searched the Cochrane Library, Pubmed, Cinalh and Narcisto identify studies that investigated risk factors in developing a VLU. The last search was performed in January 2018. Two reviewers independently reviewed the abstracts and full-text articles, and assessed the methodological quality of the included studies. Results of studies using duplex scanning, and comparing participants with and without VLUs were included in the qualitative analysis. Where possible a quantitative meta-analysis was conducted. We found five studies that investigated the relation of several risk factors with VLU development. The methodological differences of the studies made it impossible to perform a quantitative analysis. The risk factors higher age (four studies), higher body mass index (four studies), low physical activity (four studies), arterial hypertension (four studies), deep vein reflux (three studies), deep venous thrombosis (three studies) and family history of VLU (three studies) were significantly associated with a VLU in the majority of the studies. To what extent they influence the development of a VLU remains unclear because of the limited number of studies that investigated the association of these risk factors with VLU development, and the heterogeneity of these studies. Further studies are needed to confirm the association of these risk factors with the development of a VLU and to explore overweight and low physical activity in more detail.

Preoperative endoscopic pyloric balloon dilatation decreases the rate of delayed gastric emptying after Ivor-Lewis esophagectomy.

Delayed gastric emptying (DGE) after Ivor-Lewis esophagectomy occurs postoperatively in up to 50% of the patients. This pyloric dysfunction can lead to severe secondary complications postoperatively such as early aspiration, pneumonia or may even have an impact on anastomotic healing and therefore leakage. Early detection of DGE is essential to prevent further complications. The common treatment postoperatively is endoscopic pyloric balloon dilatation (EPBD) after symptoms already occurred. In our work, we analyzed patients who received a preoperative EPBD during the routine restaging endoscopy and compared those patients to a control group to analyze if preoperative EPBD may prevent postoperative DGE and secondary additional complications. We performed a single-center retrospective analysis of 115 patients who received an Ivor-Lewis esophagectomy by the same surgeon between June 2015 and October 2017. Out of these 115 patients, 91 (79.1%) patients received EPBD preoperatively during the staging/restaging endoscopy (PDG, pyloric dilatation group). In 24 (20.9%) patients, preoperative EPBD was not performed due to stenotic esophageal tumors or logistic reasons (NDG, non-pyloric dilatation group). Data of the PDG and NDG group were compared regarding the rate of postoperative DGE as well as DGE and EPBD related complications. In total, 21 (18.3%) patients developed pyloric dysfunction requiring a total of 27 EPBD during follow-up. There were 12 (13.2%) patients in the PDG and 9 (37.5%) patients in the NDG (p = 0.014), respectively. DGE-related complications such as anastomotic leaks (p = 0.466), pulmonary complications (p = 0.466) and longer median hospital stay (p = 0.685) were more frequent in the NDG group; however this difference did not reach statistical significance. The success rate for postoperative EPBD with 20-mm balloons was lower (58.5%) compared to the usage of 30-mm balloons (93.3%). All pre- and postoperative EPBD were performed without any complications. Preoperative EPBD is feasible, safe and can be combined with restating endoscopy. It seems that preoperative EPBD reduces the incidence of DGE and can prevent the need for early postoperative endoscopic interventions. Our recommendation is therefore to perform an EPBD preoperatively when possible to reduce postoperative complications to a minimum. For postoperative EPBD, we recommend the use of the 30-mm balloon due to lower redilatation rates.

Indoor allergen levels in settled airborne dust are higher in day-care centers than at home.

BACKGROUND: Early-life sensitization to indoor allergens predicts asthma development. The aim of this study was to compare allergen concentrations in day-care centers (DCC) with those in private homes. METHODS: Settled airborne dust was collected 4 times a year from 20 German DCC (620 samples) and from the homes of children and day-care workers (602 samples) using electrostatic dust collectors (EDC). The samples were analyzed with fluorescence enzyme immunoassays recognizing domestic mite allergens (DM), Fel d 1, Can f 1, and Mus m 1. Pet allergen thresholds that discriminate samples from homes with cats or dogs from those without were calculated using receiver-operating characteristics. Influences on allergen levels were analyzed using multilevel models. RESULTS: Allergen loads were on average higher in DCC than in homes. In DCC, 96% of the samples were positive for DM, 95% for Can f 1, 90% for Fel d 1, and 83% for Mus m 1. In homes, 84% contained DM, 48.5% Can f 1, 33% Fel d 1, and 43% Mus m 1. The threshold level for homes with dogs was 75 ng/m² Can f 1 (96.8% sensitivity, 96% specificity), and the threshold level for homes with cats was 46 ng/m² Fel d 1 (92% sensitivity, 94.9% specificity). In DCC, Can f 1 and Fel d 1 loads were higher than these thresholds in 37% and 54% of the samples, respectively. Allergen levels were significantly influenced by the season and room type; however, carpets on floors had no influence. CONCLUSIONS: Mite, mouse, cat, and dog allergens were mostly higher in DCC than in homes. Exposure to dog and cat allergens in DCC often reached levels of households with pets.

Periocular CO2 laser resurfacing: severe ocular complications from multiple unintentional laser impacts on the protective metal eye shields.

BACKGROUND AND OBJECTIVES: A 36-year-old woman underwent CO2 laser resurfacing for periocular rhytides using protective stainless steel Cox II ocular shields. Immediately after the treatment, corneal lesions were seen in both eyes. The left eye subsequent developed corneal ulceration and scarring, a deformed iris, cataract, and lower eye lashes showing signs of acute burns. The right cornea had a small inferior mid-peripheral superficial lesion and concomitant lower mid-peripheral burned eye lashes. Our objective was to determine the most likely cause of these ocular complications. STUDY: We estimated temperature-time combinations that could induce corneal injury and cataract. Heat conduction effects from a heated cornea to the lens and from a heated ring of periocular skin to the cornea were computed. The temperature response of a shield following CO2 laser irradiation was determined. RESULTS: We computed that cataract can develop when the corneal temperature reaches, for example, 80 °C for 14 seconds. A periocular ring of heated skin contributes little to the corneal temperature. After 7 pulses of consecutive CO2 laser bursts in 7.5 seconds, the total shield area already reached a homogeneous temperature of 63 °C. CONCLUSION: Despite uncertainties in procedural details and modeling of cataract temperatures, the eye injuries were caused beyond doubt by heating of tear-covered metal eye shields by at least 10 consecutive but unintentional laser impacts. Lasers Surg. Med. 50:980-986, 2018. © 2018 Wiley Periodicals, Inc.

Simple and rapid characterization of novel large germline deletions in SDHB, SDHC and SDHD-related paraganglioma.

Germline mutations in genes encoding subunits of succinate dehydrogenase (SDH) are associated with hereditary paraganglioma and pheochromocytoma. Although most mutations in SDHB, SDHC and SDHD are intraexonic variants, large germline deletions may represent up to 10% of all variants but are rarely characterized at the DNA sequence level. Additional phenotypic effects resulting from deletions that affect neighboring genes are also not understood. We performed multiplex ligation-dependent probe amplification, followed by a simple long-range PCR 'chromosome walking' protocol to characterize breakpoints in 20 SDHx-linked paraganglioma-pheochromocytoma patients. Breakpoints were confirmed by conventional PCR and Sanger sequencing. Heterozygous germline deletions of up to 104 kb in size were identified in SDHB, SDHC, SDHD and flanking genes in 20 paraganglioma-pheochromocytoma patients. The exact breakpoint could be determined in 16 paraganglioma-pheochromocytoma patients of which 15 were novel deletions. In six patients proximal genes were also deleted, including PADI2, MFAP2, ATP13A2 (PARK9), CFAP126, TIMM8B and C11orf57. These genes were either partially or completely deleted, but did not modify the phenotype. This study increases the number of known SDHx deletions by over 50% and demonstrates that a significant proportion of large gene deletions can be resolved at the nucleotide level using a simple and rapid method.

Is there any role for minimally invasive surgery in NET?

Neuroendocrine tumors (NET) represent the variability of almost benign lesions either secreting hormones occurring as a single lesion up to malignant lesions with metastatic potential. Treatment of NET is usually performed by surgical resection. Due to the rarity of NET, surgical treatment is mainly based on the experience and recommendations of experts and less on the basis of prospective randomized studies. In addition, the development and establishment of new surgical procedures is made more difficult by their rarity. The development of laparoscopic-assisted surgery has significantly improved the treatment of many diseases. Due to the well-known advantages of laparoscopic surgery, this method has also been increasingly used to treat NET. However, due to limited comparative data, the assumed superiority of laparoscopic surgery in the area NET remains often unclear or not yet proven. This review focuses on the present usage of laparoscopic techniques in the area of NET. Relating to the current literature, this review presents the evidence of various laparoscopic procedures for treatment of adrenal, pancreatic and intestine NET as well as extraadrenal pheochromocytoma and neuroendocrine liver metastases. Further, this review focuses on recent new developments of minimally invasive surgery in the area of NET. Here, robotic-assisted surgery and single-port surgery are promising approaches.

Perioperative α-receptor blockade in phaeochromocytoma surgery: an observational case series.

BACKGROUND: Mortality associated with surgery for phaeochromocytoma has dramatically decreased over the last decades. Many factors contributed to the dramatic decline of the mortality rate, and the influence of an α-receptor blockade is unclear and has never been tested in a randomized trial. We evaluated intraoperative haemodynamic conditions and the incidence of complications in patients with and without α-receptor blockade undergoing surgery for catecholamine producing tumours. METHODS: Haemodynamic conditions and perioperative complications were assessed in 110 patients with (B) and 166 without (N) α-receptor blockade. Data were analysed as a consecutive case series of 303 cases and subsequently via propensity score matching, and presented as mean and confidence interval (CI). RESULTS: No difference in maximal intraoperative systolic arterial pressures (B = 178 mm Hg (CI 169-187) vs N = 185 mm Hg (CI 177-193; P = 0.2542) and hypertensive episodes above 250 mm Hg were found (P = 0.7474) for the closed case series. No major complications occurred. Propensity score matching (75 pairs) revealed a significant difference of 17 mm Hg in maximal intraoperative systolic bp for these selected pairs (P = 0.024). CONCLUSIONS: Only a slight difference in mean maximal systolic arterial pressure was detected between patients with or without an α-receptor blockade. There was no difference in the incidence of excessive hypertensive episodes between groups and no major complications occurred. The basis for the general recommendation of perioperative α- receptor blockade for phaeochromocytoma surgery demands further study.

Progressive multifocal leukoencephalopathy associated with fumaric acid esters treatment in psoriasis patients.

BACKGROUND: Fumaric acid esters (FAEs) are a systemic treatment for psoriasis considered to have a favourable long-term safety profile without an increased risk for immunosuppression. However, progressive multifocal leukoencephalopathy (PML), a rare, opportunistic viral infection of the central nervous system, has been linked anecdotally to FAE treatment. OBJECTIVE: To assess clinical features and outcomes of FAE-associated PML cases. METHODS: Systematic literature search in multiple databases up to 25th February 2016 for reports of PML in psoriasis patients treated with FAEs. RESULTS: Eight cases (four male, four female) of FAE-associated PML were identified. Median age was 64 years (range 42-74 years); median FAE treatment duration was 3 years (range 1.5-5 years). Six patients were treated with a formulation containing dimethyl fumarate (DMF) and monoethyl fumarates, and two patients with a DMF formulation. Patients exhibited neurological symptoms, such as aphasia, hemiparesis and dysarthria. PML diagnosis was based on MRI findings and presence of JC virus in cerebrospinal fluid and/or brain tissue. All cases were linked to moderate-to-severe reductions in absolute lymphocyte counts, with nadirs ranging from 200 to 792 cells per mm3 . Median exposure to lymphocytopenia was 2 years (range 1-5 years). In all cases, FAE treatment was discontinued; PML was treated with mefloquine plus mirtazapine. Three patients improved, two had stable disease, two had residual symptoms, and one patient died to an immune reconstitution inflammatory syndrome. CONCLUSION: Progressive multifocal leukoencephalopathy is infrequently linked to FAE treatment, but underreporting cannot be excluded. Physicians treating patients with FAEs should be vigilant for the occurrence of PML, and both clinicians and patients should be alert for onset of new neurological symptoms. Periodic monitoring of lymphocyte counts and FAE discontinuation in case of moderate-to-severe lymphocytopenia is recommended to minimize the risk for PML.

Airway and Blood Inflammatory Markers in Waste Collectors.

Waste collectors are exposed to a heterogeneous mixture of bioaerosols able to induce health effects. The study aim was to evaluate inflammatory processes in blood and in the respiratory tract via analysis of atopy and club cell secretory protein 16 (CC16) in serum, exhaled nitric oxide (FeNO), and cellular and soluble mediators in nasal lavage fluid (NALF) and induced sputum (IS). Sixty nine current waste collectors (48% smokers) and 28 former waste collectors (25% smokers) were included in the cross-sectional study. In both groups, 63 and 64% of workers reported complaints of the eyes, nose and/or upper airways. Thirty two percent of the current and 25% of the former workers were classified as atopics. More atopics suffered from rhinitis and conjunctivitis than non-atopics (64% vs. 40% in current workers; 71% vs. 40% in former workers). CC16 values of present non-smokers were significantly higher compared to smokers. In total, FeNO values of 31 participants were lower than 10 ppb, 94% of them were smokers and 85% had respiratory symptoms of lower airways. Most of the IS biomarkers were significantly higher in smokers than in non-smokers. Non-smoking workers with respiratory symptoms of lower airways had slightly elevated mediator IS concentrations compared to asymptomatic non-smokers. We conclude that inflammatory changes in waste collectors are detectable in the content of IS biomarkers, exhaled NO, and serum CC16, which all are influenced by the smoking habit. No significant differences in biomarkers are detectable between current and former waste collectors.

Liquid-based versus conventional cytology of oral brush biopsies: a split-sample pilot study.

OBJECTIVE: The aim of this prospective split sample study was to evaluate the applicability of liquid-based cytology (LBC) of oral brush biopsies for detection of oral cancer. METHODS: Two different preparation techniques were investigated: the conventional transfer procedure to glass slides and the LBC preparation method. The obtainments of epithelial cells were performed five times with a nylon brush and transferred onto five glass slides. Additionally, the brushes, which were normally discarded, were stored in a fixative solution. Conventional slides and respective thin layers from a total of 113 cases were reviewed with both techniques. RESULTS: Thin layers showed excellent morphology on a clear background, which allowed an accurate diagnosis. In contrast, the conventional glass slides showed significantly more blood contamination and cell overlapping. The sensitivity of conventional cytological diagnosis was 96.3%, the specificity archived 90.6%, the positive predictive value was 96.3% and the negative predictive value scored 90.6%. The sensitivity of the cytological diagnosis using thin layers archived 97.5%, the specificity was 68.8%, the positive predictive value revealed 88.76% and negative predictive value was 91.7%. CONCLUSION: Our findings indicate that in oral cytology, LBC may replace other types of wet-fixed preparations using the full amount of collected cells, resulting in enhanced specimen quality archiving comparable values of diagnostic accuracy. CLINICAL RELEVANCE: LBC facilitates the cell collection due to simpler handling and less transfer errors by dentists and may improve the overall diagnostic accuracy of oral brush biopsies in future.

Efficacy, effectiveness and safety of fumaric acid esters in the treatment of psoriasis: a systematic review of randomized and observational studies.

Fumaric acid esters (FAEs) are increasingly used as a systemic treatment for psoriasis, but there are still uncertainties regarding their suitability. The objective of this systematic review was to assess the evidence for the efficacy and safety of FAEs in psoriasis treatment. A systematic literature search was performed in seven databases up to 17 August 2015. Inclusion criteria were studies that reported clinical effects of FAEs in patients with psoriasis without restrictions in study design, language or publication date. Methodological quality of randomized controlled trials (RCTs) and overall level of quality were assessed using the Cochrane risk of bias tool and the Grading of Recommendation, Assessment, Development and Evaluation approach, respectively. A total of 68 articles were included. There were seven RCTs (total 449 patients) that had an unclear risk of bias and were too clinically heterogeneous to allow a meta-analysis. Overall, mean Psoriasis Area and Severity Index decreased by 42-65% following 12-16 weeks of treatment. There were 37 observational studies (a total of 3457 patients) that supported the RCT findings, but most were uncontrolled with a high risk of bias. Commonly reported adverse events included gastrointestinal complaints and flushing, leading to treatment withdrawal in 6-40% of patients. Several case-reports described rare adverse events, such as renal Fanconi syndrome and progressive multifocal leukoencephalopathy. There was a lack of studies focusing on long-term use and comparisons with other treatments. This review concluded that there is low-quality evidence to recommend the use of oral FAEs to treat plaque psoriasis in adult patients. Studies focusing on long-term safety and comparison with systemic psoriasis treatments could lead to a better understanding of the role of FAEs as a treatment for psoriasis.

Reliability of diagnosis from Mohs slides: interpersonal and intrapersonal agreement on basal cell carcinoma presence and histological subtype.

BACKGROUND: The success of Mohs micrographic surgery (MMS) depends partly on the correct diagnosis of slides. OBJECTIVES: To determine reliability of diagnosis from Mohs slides. METHODS: This was a prospective study evaluating the reliability of diagnosis from Mohs slides of basal cell carcinoma (BCC) presence, BCC location on the slide and BCC subtype among six raters who independently assessed 50 Mohs slides twice with a 2-month interval. Slides were randomly selected whereby difficult-to-diagnose slides were oversampled. For each slide, a reference diagnosis was established by an expert panel. Cohen's kappa (κ) was calculated to determine levels of agreement interpersonally (rater vs. reference diagnosis) and intrapersonally (rater at T1 vs. T2). Multivariable logistic regression was used to determine independent risk factors for slides with interpersonal discordant diagnosis. The variables studied were BCC presence, whether a slide was scored as easy or difficult to diagnose, review duration of the 50 slides, profession and years of experience in diagnosis from Mohs slides. RESULTS: Interpersonal and intrapersonal agreement were substantial on BCC presence (κ = 0·66 and 0·68) and moderate on BCC subtype (κ = 0·45 and 0·55). Slides that were scored as difficult to diagnose were an independent risk factor for interpersonal discordant diagnosis on BCC presence (odds ratio 3·54, 95% confidence interval 1·81-6·84). CONCLUSIONS: Reliability of diagnosis from Mohs slides was substantial on BCC presence and moderate on BCC subtype. For slides that are scored difficult to diagnose, a second opinion is recommended to prevent misinterpretation and thereby recurrence of skin cancer.

Effects of bioaerosol exposure on respiratory health in compost workers: a 13-year follow-up study.

OBJECTIVES: To determine the risk of German compost workers developing chronic respiratory effects from long-term exposure to bioaerosols. METHODS: Respiratory health was determined in 74 currently exposed compost workers and 37 non-exposed controls after 13 years of follow-up. In addition, 42 former compost workers (drop-outs) who left their work during the follow-up period were also examined. Respiratory symptoms and working conditions were assessed using identical questionnaires as at baseline. In addition, lung function was measured using the same spirometer as in the initial study. Sera from both surveys were tested for specific IgE and IgG antibodies to moulds and the risk of work-related symptoms was evaluated using regression approaches for prospective studies with binary data. RESULTS: In the follow-up period, the number of participants reporting cough significantly increased in compost workers and drop-outs compared to the controls. Working as a compost worker for at least 5 years increased the relative risk for cough (RR 1.28; 95% CI 1.2 to 1.4) and for cough with phlegm (RR 1.32; 95% CI 1.2 to 1.5). Current and former compost workers had slightly lower predicted percentage of forced expiratory volume in 1 s and predicted percentage of forced vital capacity than controls, but decrease in lung function during follow-up was not different among the 3 groups. In addition, no significant changes could be detected in antibody concentrations. CONCLUSIONS: Our results suggest that chronic exposure to bioaerosols in composting plants is related to a significantly higher risk for cough with phlegm, indicating chronic bronchitis. However, compost workers showed no higher incidence of deterioration of pulmonary function over the study.

Long-lived coherence in pentafluorobenzene as a probe of ππ(*) - πσ(*) vibronic coupling.

The dynamics of pentafluorobenzene after femtosecond laser excitation to the optically bright ππ(*) first excited electronic state have been investigated by femtosecond time-resolved time-of-flight mass spectrometry and femtosecond time-resolved photoelectron imaging spectroscopy. The observed temporal profiles exhibit a bi-exponential decay behavior with a superimposed, long-lived, large-amplitude oscillation with a frequency of νosc = 78-74 cm(-1) and a damping time of τD = 5-2 ps. On the basis of electronic structure and quantum dynamics calculations, the oscillations have been shown to arise due to vibronic coupling between the optically bright ππ(*) state and the energetically close-lying optically dark πσ(*) state. The coupling leads to a pronounced double-well character of the lowest excited adiabatic potential energy surface along several out-of-plane modes of b1 symmetry. The optical electronic excitation initiates periodic wavepacket motion along these modes. In the out-of-plane distorted molecular configuration, the excited state acquires substantial πσ(*) character, thus modulating the ionization probability. The photoelectron spectra and the anisotropy of their angular distribution confirm the periodically changing electronic character. The ionizing probe laser pulse directly maps the coupled electron-nuclear motion into the observed signal oscillations.

[Cognitive Development in Children with Benign Rolandic Epilepsy of Childhood with Centrotemporal Spikes - Results of a Current Systematic Database Search]. / Kognitive Entwicklung von Kindern mit benigner Epilepsie des Kindesalters mit zentrotemporalen Spitzen (Rolando-Epilepsie) ­ Ergebnisse einer aktuellen systematischen Literaturrecherche.

Benign Rolandic Epilepsy (BRE) is one of the most common epilepsy syndromes in childhood. Although global intellectual performance is typically normal in BRE-patients, problems were found in specific cognitive domains. To summarize recent empirical findings concerning cognitive development in children with BRE a systematic literature search of clinical studies published between 2009 and 2015 was performed. 19 studies of relevance were found.In most recent studies children with BRE consistently showed general intellectual performance within the normal range. However, in two of the studies patients showed a significantly poorer (but still normal) performance in comparison to controls. The studies provide clear indications for a high prevalence of impairments in language (10 out of 12 studies) and academic performance (6 out of 8 studies) in children with BRE. Regarding deficits in other cognitive domains (attention, memory, visual/auditory perception, executive functions) current findings are inconsistent. In addition, no clear results are found in studies examining cognitive development after remission of BRE. Studies on the relationship between selected clinical/electroencephalographic characteristics (e. g. EEG-patterns, focus lateralization) and cognitive performance and studies on potential benefits of anti-epileptic therapy for cognitive functions also have not yielded consistent results. Studies using fMRI and evoked potentials provide evidence for functional reorganization of neural networks in BRE.Due to the developmental risks in children with BRE early cognitive assessment, early treatment and follow-up assessments are important.

Five-year results of a randomized clinical trial of conventional surgery, endovenous laser ablation and ultrasound-guided foam sclerotherapy in patients with great saphenous varicose veins.

BACKGROUND: A variety of techniques exist for the treatment of patients with great saphenous vein (GSV) varicosities. Few data exist on the long-term outcomes of these interventions. METHODS: Patients undergoing conventional surgery, endovenous laser ablation (EVLA) and ultrasound-guided foam sclerotherapy (UGFS) for GSV varicose veins were followed up for 5 years. Primary outcome was obliteration or absence of the treated GSV segment; secondary outcomes were absence of GSV reflux, and change in Chronic Venous Insufficiency quality-of-life Questionnaire (CIVIQ) and EuroQol - 5D (EQ-5D™) scores. RESULTS: A total of 224 legs were included (69 conventional surgery, 78 EVLA, 77 UGFS), 193 (86.2 per cent) of which were evaluated at final follow-up. At 5 years, Kaplan-Meier estimates of obliteration or absence of the GSV were 85 (95 per cent c.i. 75 to 92), 77 (66 to 86) and 23 (14 to 33) per cent in the conventional surgery, EVLA and UGFS groups respectively. Absence of above-knee GSV reflux was found in 85 (73 to 92), 82 (72 to 90) and 41 (30 to 53) per cent respectively. CIVIQ scores deteriorated over time in patients in the UGFS group (0.98 increase per year, 95 per cent c.i. 0.16 to 1.79), and were significantly worse than those in the EVLA group (-0.44 decrease per year, 95 per cent c.i. -1.22 to 0.35) (P = 0.013). CIVIQ scores for the conventional surgery group did not differ from those in the EVLA and UGFS groups (0.44 increase per year, 95 per cent c.i. -0.41 to 1.29). EQ-5D™ scores improved equally in all groups. CONCLUSION: EVLA and conventional surgery were more effective than UGFS in obliterating the GSV 5 years after intervention. UGFS was associated with substantial rates of GSV reflux and inferior CIVIQ scores compared with EVLA and conventional surgery. REGISTRATION NUMBER: NCT00529672 (http://www.clinicaltrials.gov).

Addition of an oral histamine antagonist to reduce adverse events associated with fumaric acid esters in the treatment of psoriasis: a randomized double-blind placebo-controlled trial.

BACKGROUND: Fumaric acid esters (FAEs) are considered an effective and safe long-term treatment for psoriasis. However, 30-40% of patients need to discontinue FAE treatment due to intolerable adverse events. OBJECTIVES: To assess whether the addition of cetirizine, an oral histamine-1 receptor antagonist, to FAEs would reduce the incidence of adverse events. METHODS: In a randomized, double-blind, placebo-controlled trial, patients with psoriasis with a Psoriasis Area and Severity Index ≥ 10 starting an FAE up to a dose of dimethylfumarate 720 mg per day were randomized 1 : 1 to receive either additional cetirizine 10 mg once daily (n = 25) or placebo (n = 25) for 12 weeks. Randomization and treatment allocation were done at our hospital trial pharmacy. Primary outcomes were the incidence of adverse events and the proportion of patients discontinuing treatment. RESULTS: Fifty patients (33 male, 17 female; median age 44 years) were enrolled. Addition of cetirizine did not reduce the incidence of adverse events compared with placebo (84% vs. 84%, P = 1·00). The types of adverse events were not different between the cetirizine and placebo groups, the most common being gastrointestinal complaints (68% vs. 64%) and flushes (60% vs. 48%). The proportion of patients discontinuing treatment was not statistically different between the cetirizine and placebo groups (24% vs. 32%, P = 0·53). CONCLUSIONS: Addition of oral cetirizine 10 mg once daily to FAE treatment did not reduce adverse events in patients with psoriasis during the first 12 weeks of treatment. The mechanisms underlying FAE-induced gastrointestinal and flushing symptoms likely involve mediators other than histamine.