Massive intraventricular haemorrhage from aneurysmal rupture: patient proportions and eligibility for intraventricular fibrinolysis

Massive intraventricular haemorrhage (IVH) complicating aneurysmal subarachnoid haemorrhage (SAH) is associated with a poor prognosis. Small observational studies suggest favourable results from fibrinolysis of the intraventricular blood. We performed an observational study on IVH in a large series of patients with SAH to assess the proportion of patients that may benefit from fibrinolytic treatment. From our prospective database we retrieved patients with aneurysmal SAH admitted between January 2000 and January 2005. We calculated the proportion of patients with massive IVH and the proportion of patients that are eligible for fibrinolysis on basis of clinical and CT-scan characteristics and assessed neurological outcome in a treatment strategy without fibrinolysis. Poor neurological condition was defined as World Federation of Neurological Surgeons scale 4 and 5, poor outcome as death or dependence 3 months after SAH. Of the 573 patients admitted with aneurysmal SAH, 59 (10%; 95% confidence interval CI 8–13%) had massive IVH, of which 55 were in poor clinical condition. For these 55 patients, the case-fatality rate was 78% (95% CI 66–88%) and the proportion with poor outcome 91% (95% CI 81–97%). Of the 55 patients, 31 (56%, and 5% of all patients SAH within the study period) fulfilled our eligibility criteria and were considered suitable for intraventricular fibrinolysis. At 3 months, 30 of these 31 eligible patients (97%; 95% CI 85–100%) had a poor outcome. Massive IVH occurs in 10% of patients with aneurysmal SAH. Half of these patients may benefit from intraventricular fibrinolysis. Without fibrinolysis outcome is almost invariably poor in these patients

Cost-Effectiveness of Lower Extremity Nerve Decompression Surgery in the Prevention of Ulcers and Amputations:A Markov Analysis

Background: The costs and health effects associated with lower extremity complications in diabetes mellitus are an increasing burden to society. In selected patients, lower extremity nerve decompression is able to reduce symptoms of neuropathy and the concomitant risks of diabetic foot ulcers and amputations. To estimate the health and economic effects of this type of surgery, the cost-effectiveness of this intervention compared to current nonsurgical care was studied. Methods: To estimate the incremental cost-effectiveness of lower extremity nerve decompression over a 10-year period, a Markov model was developed to simulate the onset and progression of diabetic foot disease in patients with diabetes and neuropathy who underwent lower extremity nerve decompression surgery, compared to a group undergoing current nonsurgical care. Mean survival time, health-related quality of life, presence or risk of lower extremity complications, and in-hospital costs were the outcome measures assessed. Data from the Rotterdam Diabetic Foot Study were used as current care, complemented with information from international studies on the epidemiology of diabetic foot disease, resource use, and costs, to feed the model. Results: Lower extremity nerve decompression surgery resulted in improved life expectancy (88,369.5 life-years versus 86,513.6 life-years), gain of quality-adjusted life-years (67,652.5 versus 64,082.3), and reduced incidence of foot complications compared to current care (490 versus 1087). The incremental cost-effectiveness analysis was -euro59,279.6 per quality-adjusted life-year gained, which is below the Dutch critical threshold of less than euro80,000 per quality-adjusted life-year. Conclusions: Decompression surgery of lower extremity nerves improves survival, reduces diabetic foot complications, and is cost saving and cost-effective compared with current care, suggesting considerable socioeconomic benefit for society

Item reduction of the 39-item Rotterdam Diabetic Foot Study Test Battery using decision tree modelling

Aims: Pedal sensory loss due to diabetes-related neuropathy can be graded by testing static two-point discrimination (S2PD), moving two-point discrimination (M2PD), static one-point discrimination (S1PD; eg, 10-g monofilament), and vibration sense and is included in the Rotterdam Diabetic Foot (RDF) Study Test Battery. The aim of this study is to investigate if decision tree modelling is able to reduce the number of tests needed in estimating pedal sensation. Methods: The 39-item RDF Study Test Battery (RDF-39) scores were collected from the prospective RDF study and included baseline (n = 416), first follow-up (n = 364), and second follow-up (n = 135) measurements, supplemented with cross-sectional control data from a previous study (n = 196). Decision tree analysis was used to predict total RDF-39 scores using individual test item data. The tree was developed using baseline RDF study data and validated in follow-up and control data. Spearman correlation coefficients assessed the reliability between the decision tree and original RDF-39. Results: The tree reduced the number of items from 39 to 3 in estimating the RDF-39 sum score. M2PD (hallux), S2PD (first dorsal web, fifth toe), vibration sense (interphalangeal joint), and S1PD (first dorsal web, fift

Terpene synthase genes originated from bacteria through horizontal gene transfer contribute to terpenoid diversity in fungi

Fungi are successful eukaryotes of wide distribution. They are known as rich producers of secondary metabolites, especially terpenoids, which are important for fungi-environment interactions. Horizontal gene transfer (HGT) is an important mechanism contributing to genetic innovation of fungi. However, it remains unclear whether HGT has played a role in creating the enormous chemical diversity of fungal terpenoids. Here we report that fungi have acquired terpene synthase genes (TPSs), which encode pivotal enzymes for terpenoid biosynthesis, from bacteria through HGT. Phylogenetic analysis placed the majority of fungal and bacterial TPS genes from diverse taxa into two clades, indicating ancient divergence. Nested in the bacterial TPS clade is a number of fungal TPS genes that are inferred as the outcome of HGT. These include a monophyletic clade of nine fungal TPS genes, designated as BTPSL for bacterial TPS-like genes, from eight species of related entomopathogenic fungi, including seven TPSs from six species in the genus Metarhizium. In vitro enzyme assays demonstrate that all seven BTPSL genes from the genus Metarhizium encode active enzymes with sesquiterpene synthase activities of two general product profiles. By analyzing the catalytic activity of two resurrected ancestral BTPSLs and one closely related bacterial TPS, the trajectory of functional evolution of BTPSLs after HGT from bacteria to fungi and functional divergence within Metarhizium could be traced. Using M. brunneum as a model species, both BTPSLs and typical fungal TPSs were demonstrated to be involved in the in vivo production of terpenoids, illustrating the general importance of HGT of TPS genes from bacteria as a mechanism contributing to terpenoid diversity in fungi

(Cost-)effectiveness of lower extremity nerve decompression surgery in subjects with diabetes:the DeCompression (DECO) trial-study protocol for a randomised controlled trial

Introduction The peripheral nerves of patients with diabetes are often pathologically swollen, which results in entrapment at places of anatomical narrowing. This results in nerve dysfunction. Surgical treatment of compression neuropathies in the lower extremities (lower extremity nerve decompression (LEND)) results in relief of symptoms and gain in peripheral nerve function, which may lead to less sensory loss (short term) and less associated detrimental effects including foot ulceration and amputations, and lower costs (long term). The aim of the DeCompression trial is to evaluate the effectiveness and (cost-)effectiveness of surgical decompression of compressed lower extremity nerves (LEND surgery) compared with patients treated with conventional (non-surgical) care. Methods and analysis A stratified randomised (1 to 1) controlled trial comparing LEND surgery (intervention) with conventional non-surgical care (control strategy) in subjects with diabetes with problems of neuropathy due to compression neuropathies in the lower extremity. Randomisation is stratified for participating hospital (n=11) and gender. Patients and controls have the same follow-up at 1.5, 3, 6, 9, 12, 18, 24 and 48 months. Participants (n=344) will be recruited in 12 months and enrolled in all affiliated hospitals in which they receive both the intervention or conventional non-surgical care and follow-up. Outcome assessors are blinded to group assignment. Primary outcome: disease-specific quality of life (Norfolk Quality of Life Questionnaire-Diabetic Neuropathy). Secondary outcomes: health-related quality of life (EuroQoL 5-dimension 5-level (EQ-5D5L), 36-item Short Form (SF-36)), plantar sensation (Rotterdam Diabetic Foot Test Battery), incidence of ulcerations/amputations, resource use and productivity loss (Medical Cost Questionnaire, Productivity Cost Questionnaire) during follow-up. The incremental cost-effectiveness ratio will be estimated on the basis of the collected empirical data and a cost-utility model. Ethics and dissemination Ethics approval has been granted by the Medical Research Ethics Committee of Utrecht University Medical Center (reference: NL68312.041.19v5, protocol number: 19-335/M). Dissemination of results will be via journal articles and presentations at national and international conferences

Irinotecan-Induced Dysarthria

Colorectal carcinomas are among the most common tumor types and are generally treated with palliative chemotherapy in case of metastatic disease. Here, we describe the case of a 46-year-old patient with metastatic rectal carcinoma who received second-line therapy with irinotecan and developed isolated transient dysarthria (with normal MR imaging of the brain) following each administration of irinotecan. Neurological and logopedical evaluation revealed that the dysarthria predominantly resulted from a reduced capacity in fine-tuning of motor functions of the tip of the tongue and a minimal reduction in the power of speech at labiodental contact. As hypoglossal nerve activity has been reported to be especially susceptible to cholinergic stimulation and irinotecan can cause cholinergic side effects by binding to and inactivating acetylcholinesterase, we suspect this mechanism to be responsible for irinotecan-induced dysarthria