FUS pathology defines the majority of tau- and TDP-43-negative frontotemporal lobar degeneration

Through an international consortium, we have collected 37 tau- and TAR DNA-binding protein 43 (TDP-43)-negative frontotemporal lobar degeneration (FTLD) cases, and present here the first comprehensive analysis of these cases in terms of neuropathology, genetics, demographics and clinical data. 92% (34/37) had fused in sarcoma (FUS) protein pathology, indicating that FTLD-FUS is an important FTLD subtype. This FTLD-FUS collection specifically focussed on aFTLD-U cases, one of three recently defined subtypes of FTLD-FUS. The aFTLD-U subtype of FTLD-FUS is characterised clinically by behavioural variant frontotemporal dementia (bvFTD) and has a particularly young age of onset with a mean of 41 years. Further, this subtype had a high prevalence of psychotic symptoms (36% of cases) and low prevalence of motor symptoms (3% of cases). We did not find FUS mutations in any aFTLD-U case. To date, the only subtype of cases reported to have ubiquitin-positive but tau-, TDP-43- and FUS-negative pathology, termed FTLD-UPS, is the result of charged multivesicular body protein 2B gene (CHMP2B) mutation. We identified three FTLD-UPS cases, which are negative for CHMP2B mutation, suggesting that the full complement of FTLD pathologies is yet to be elucidated

Mini nutritional assessment and mortality after hip fracture surgery in the elderly

Background: Hip fracture surgery in elderly patients is associated with a poor postoperative outcome and a high mortality. Malnutrition is a frequent problem in elderly patients and may be associated with mortality after hip fracture surgery. The Mini Nutritional Assessment (MNA) is a valuable tool to identify malnourished patients and those at risk for malnutrition. Objective: To evaluate the association between the preoperative MNA score and mortality after surgery for hip fractures in elderly patients. Methods: Patients with a hip fracture and an indication for surgery were included in our study. This study was part of a randomized trial on the effect of taurine on postoperative outcome in elderly hip fracture patients. The MNA was assessed on admission before surgery. Length of stay, postoperative complications and mortality were documented. The association of the MNA score on postoperative outcome and mortality was analyzed using Cox regression analysis. Results: The one-year survival rate in 226 elderly hip fracture patients was 79%. In-hospital mortality rates and 1-year mortality were 27% and 46% in malnourished patients, 12% and 26% in patients at risk for malnutrition and 7% and 17% in well-nourished patients as assessed by MNA. Conclusion: Preoperative malnutrition measured by the MNA is associated with mortality in elderly hip fracture patients

Effects of reintegration activities on the Dutch labour market, regarding several levels of education

In the Netherlands during the early nineteen nineties social security administration offices and labour exchange offices decided to co-operate. Goal of this cooperation is to support the reintegration of unemployed people into the labour market and to shorten the individual spells of unemployment. As a result of the cooperation information is available about levels of education of the unemployed. This article primarely focuses on the effects of reintegration activities on the duration of unemployment for different levels of education. Results of the analysis are compared with the human capital theory. Also the question is discussed whether within the framework of the cooperation persons with a higher level of education have shorter spells of unemployment. Finally there is an analysis of the effects of activities undertaken by the unemployed themselves to find a job. People with a university degree have significant longer spells of unemployment. The reintegration activities of the social security administration offices shorten unemployment durations significantly for this group only. Activities undertaken by the unemployed themselves shorten the spells of unemployment for lower educated people (only primary education) and for persons with higher general secondary/secondary/intermediate vocational education as highest completed education.

Impact of Body Composition on Surgical Outcome in Rectal Cancer Patients, a Retrospective Cohort Study

Background: Obesity is becoming a bigger health problem every year. Current research shows that the obesity-related metabolic problems are strongly associated with visceral fat and not subcutaneous fat. Visceral obesity (VO) is associated with a worse postoperative outcome in multiple fields of abdominal surgery. On the other hand, muscle mass is related to better postoperative outcome. In rectal cancer patients, we studied the influence of visceral obesity and muscle mass on postoperative complications. Methods: The visceral fat area (VFA) and skeletal muscle area (SMA) were determined on preoperative CT scans in 406 patients. The preoperative comorbidity, per-operative outcome and postoperative complications were extracted retrospectively from the patient files. VO was defined as a VFA > 100 cm2. Correlations between body composition, postoperative complications and LOS were studied. Results: In our study, 67% of the patients were classified as visceral obese. Mean body mass index (BMI) was higher in the VO group (26.6 ± 3.5 vs 23.5 ± 2.8; p < 0.001). Visceral obese patients had a higher prevalence of cardiac comorbidity (29% vs 13% p = 0.001), hypertension (36% vs 20% p = 0.002) and diabetes mellitus (16% vs 5% p = 0.002). In addition, VO patients had more operative blood loss (431 vs 310 mL; p = 0.008), longer operating time (166 vs 149 min p = 0.003) and more wound infections (14% vs 8% p = 0.048). Visceral obesity was associated with more complications (OR: 1.63 p = 0.043) and longer LOS (risk estimate: 1.18 p = 0.009). Conclusion: VO patients more often had a history of cardiac disease, hypertension and diabetes mellitus. Visceral obesity correlated with a worse outcome after surgery for rectal cancer

Preoperative Methods to Reduce Liver Volume in Bariatric Surgery: a Systematic Review

# The Author(s) 2015. This article is published with open access at Springerlink.com Background Patients qualified for gastric bypass surgery have an enlarged and fatty liver. An essential step in gastric bypass surgery is elevation of the left liver lobe to expose the gastro-esophageal junction. An enlarged and fatty liver complicates the surgical procedure and increases the risk for laceration of the liver. The aim of our study was to evaluate methods to reduce liver volume in patients prior to gastric bypass surgery. Methods A systematic literature search of multiple databases, including PubMed, EMBASE.com, and the Cochrane Library and a hand search of reference lists, was performed. We used the search terms morbid obesity and liver, including their syn-onyms and controlled terms. Inclusion criteria were as fol-lows: patients with morbid obesity who qualified for bariatric surgery, the use of a preoperative treatment to reduce liver volume, and the use of imaging techniques before and after treatment. Results In total, 281 patients in 11 different studies were in-cluded. Preoperative diets reduced liver size by an average of 14 %, alternative methods including nutritional supplements, reduced liver size between 20 and 43 %, and an intragastric balloon by 32 %. Conclusions This review showed that nutritional supplements and intragastric balloon are more effective than low calorie diets in reducing liver volume prior to gastric bypass surgery. However, low calorie diet is the preferable method to reduce liver volume, considering the level of evidence and practical applicability. There is a need for well-designed randomized studies with sufficient power in order to confirm the effective-ness of preoperative methods to reduce liver volume

The BATTLE study: Effects of long-term tobramycin inhalation solution (TIS) once daily on exacerbation rate in patients with non-cystic fibrosis bronchiectasis. Study protocol of a double blind, randomized, placebo-controlled trial: study protocol

Background: Patients with bronchiectasis typically suffer from chronic symptoms such as a productive cough with or without exacerbations leading to hospitalization, causing reduced quality of life (QoL) and mortality. Long-term inhaled antibiotics to treat chronic bronchial infection is registered for use in cystic fibrosis (CF) bronchiectasis. However, in patients with non-CF bronchiectasis data on long-term antibiotics are limited. Objective: To investigate the effectiveness of maintenance tobramycin inhalation solution (TIS) in bronchiectasis patients without cystic fibrosis. Study design: The BATTLE study is a randomized, double blind placebo controlled, multicenter study in the Netherlands performed in patients aged ?18-year-old with confirmed bronchiectasis, at least two exacerbations in the preceding year, and minimal one positive sputum culture with gram negative pathogens or Staphylococcus aureus, sensitive to tobramycin in the preceding year and at baseline. Patients will be treated with TIS once daily (OD) or placebo (saline 0.9%) OD for 52 weeks followed by a run-out period of 4 weeks after the last dose. The primary outcome is the yearly rate of pulmonary exacerbations. Among secondary outcome parameters are time to exacerbation, lung function, QoL, microbiological evaluation and safety. Discussion: The BATTLE study is designed to determine the efficacy and safety of maintenance TIS OD in bronchiectasis patients colonized by different pathogens and could lead to important new evidence for TIS therapy in this population. The BATTLE study is registered in Clinical trials.gov with registration number: NCT02657473

The effect of azithromycin on sputum inflammatory markers in bronchiectasis

Abstract Background Long term macrolide treatment has been found beneficial in bronchiectasis (BE) -pathogical bronchial dilatation- possibly due to a combined anti-bacterial and immunomodulatory effect. The exact mechanism of inflammatory response is unknown. Here, we investigated the effect of maintenance macrolide treatment on the inflammatory response in BE. In addition, we assessed the inflammatory profile in BE in relation to disease severity. Methods During the BAT randomized controlled trial (investigating the effect of 1 year of azithromycin (AZM) in 83 BE patients), data on BE severity, lung function and sputum microbiology was collected. For the current study, a wide range of inflammatory markers were analysed in 3- monthly sputum samples in all participants. Results At baseline, marked neutrophilic but also eosinophilic inflammation was present in both groups, which remained stable throughout the study and was not affected by AZM treatment. Significant upregulation of pro-inflammatory markers correlated with FEV1 < 50% (TNFα, ECP, IL-21, IL-1, p = 0.01- 0.05), H. influenzae (HI) colonization (MPO, ECP, MIP-1, TNFα, IL-21, Il-8, IL-1, IL-1α, p < 0.001 – 0.04) and number of exacerbations (MPO, ECP, VEGF, MMP-9, p = 0.003 – 0.01). Surprisingly, colonization with P. aeruginosa (PA) was found to correlate with an attenuated inflammatory response compared to non-PA colonized. In placebo-treated patients, presence of an infectious exacerbation was reflected by a significant excessive increase in inflammation as compared to a non-significant upregulation in the AZM-treated patients. Conclusion One year of AZM treatment did not result in attenuation of the inflammatory response in BE. Increasing disease severity and the presence of an exacerbation were reflected by upregulation of pro-inflammatory markers