Use of augmented reality for image-guided spine procedures

European Spine Journal - Because of its ability to superimpose imaging data on a patient, while anchoring the user’s view to the immediate surroundings, augmented reality (AR) has the...     

Real-world outcomes following 12 months of intravitreal aflibercept monotherapy in patients with diabetic macular edema in France: results from the APOLLON study

Graefe's Archive for Clinical and Experimental Ophthalmology - To report the effectiveness of intravitreal aflibercept (IVT-AFL) treatment for diabetic macular edema (DME) in French clinical...     

Accuracy of sentinel node biopsy in esophageal carcinoma: a systematic review and meta-analysis of the pertinent literature

The use of sentinel node surgery for esophageal carcinoma is still under investigation. We evaluated the data available in the literature on this topic, and herein present the results in a systematic review format. PUBMED, SCOPUS, the ISI web of knowledge and the information from the annual meetings of the Japan Esophageal Society were searched using the search terms: “(esophagus OR esophageal) AND sentinel”. The outcomes of interest were the detection rate and sensitivity. Overall, 18 studies were included. The pooled detection rate was 89.2 % [82.6–93.5]. Patients with T1 and two tumors had a 17 % higher detection rate compared to those with T3 and four tumors. The pooled sensitivity was 84 % [78–88 %]. The sensitivity was higher for adenocarcinoma compared to squamous cell carcinoma (SCC) (91 vs. 81 %). In the SCC patients, there was a trend toward decreased sensitivity associated with an increasing tumor depth (T1:88 %, T2:76 %, T3:50 %). Our analysis indicated that sentinel node biopsy is useful in adenocarcinoma patients. For SCC patients, including only cN0 patients (preferably T1 and 2) would increase the detection rate and sensitivity. Due to the limited number of high-quality studies, drawing any more definite conclusions is impossible. Large cohort studies with a standardized and consistent design will be needed in the future.     

Comparing barriers to mental health treatment and substance use disorder treatment among individuals with comorbid major depression and substance use disorders

Barriers to both mental health and substance use disorder treatments have rarely been examined among individuals with comorbid mental health and substance use disorders. In a sample of 393 adults with 12-month major depressive episodes and substance use disorders, we compared perceived barriers to these two types of treatments. Data were drawn from the 2005–2011 US National Surveys on Drug Use and Health. Overall, the same individuals experienced different barriers to mental health treatment versus substance use disorder treatment. Concerns about negative views of the community, effects on job, and inconvenience of services were more commonly reported as reasons for not receiving substance use disorder treatment. Not affording the cost of care was the most common barrier to both types of treatments, but more commonly reported as a barrier to mental health treatment. Improved financial access through the Affordable Care Act and parity legislation and integration of mental health and substance use disorder services may help to reduce treatment barriers among individuals with comorbid mental health and substance disorders.     

Chronic suppression of insulin by diazoxide alters the activities of key enzymes regulating hepatic gluconeogenesis in Zucker rats

OBJECTIVES: Chronic attenuation of hyperinsulinemia by diazoxide (DZ), an inhibitor of glucose-mediated insulin secretion, improved insulin sensitivity and glucose tolerance and caused down-regulation of lipid metabolizing enzymes in adipose tissue and decreased the rate of weight gain in mildly hyperglycemic obese Zucker rats. Since the liver plays a central role in glucose homeostasis, we studied the effect of chronic insulin suppression on key insulin-sensitive enzymes regulating hepatic gluconeogenesis. METHODS: DZ (150 mg/kg per day) or vehicle (control) was administered to 7-week-old female obese and lean Zucker rats for a period of 4 weeks. RESULTS: DZ-treated animals showed lower fasting plasma insulin levels (P<0.001) than their controls. Plasma glucose levels were lower in DZ obese rats than in controls (P<0.001), without a significant change in DZ lean animals. DZ had no effect on glucose transporter 2 protein expression in either strain. DZ treatment resulted in lower hepatic glucokinase (P<0.001) and glucose-6-phosphatase (P<0.0001) and phosphoenolpyruvate carboxykinase (PEPCK) activities only in obese rats compared with controls (P<0.001). However, DZ-treated lean rats demonstrated higher PEPCK activity than controls (P<0.002). DZ-treated animals demonstrated enhanced hepatic glucose-6-phosphate content (P<0.01), glycogen synthase activity (P<0.0001) and glycogen content (P<0.02) compared with their controls despite increased hepatic glycogen phosphorylase a activity in these animals (P<0.02). CONCLUSIONS: Chronic suppression of hyperinsulinemia in obese Zucker rats by DZ decreased the activities of key enzymes regulating hepatic gluconeogenesis, implying that attenuation of the hyperinsulinemic state by DZ may be therapeutically beneficial.     

Glutamate Dysfunction Associated with Developmental Cerebellar Damage: Relevance to Autism Spectrum Disorders

Neural abnormalities commonly associated with autism spectrum disorders include prefrontal cortex (PFC) dysfunction and cerebellar pathology in the form of Purkinje cell loss and cerebellar hypoplasia. It has been reported that loss of cerebellar Purkinje cells results in aberrant dopamine neurotransmission in the PFC which occurs via dysregulation of multisynaptic efferents from the cerebellum to the PFC. Using a mouse model, we investigated the possibility that developmental cerebellar Purkinje cell loss could disrupt glutamatergic cerebellar projections to the PFC that ultimately modulate DA release. We measured glutamate release evoked by local electrical stimulation using fixed-potential amperometry in combination with glutamate selective enzyme-based recording probes in urethane-anesthetized Lurcher mutant and wildtype mice. Target sites included the mediodorsal and ventrolateral thalamic nuclei, reticulotegmental nuclei, pedunculopontine nuclei, and ventral tegmental area. With the exception of the ventral tegmental area, the results indicated that in comparison to wildtype mice, evoked glutamate release was reduced in Lurcher mutants by between 9 and 72 % at all stimulated sites. These results are consistent with the notion that developmental loss of cerebellar Purkinje cells drives reductions in evoked glutamate release in cerebellar efferent pathways that ultimately influence PFC dopamine release. Possible mechanisms whereby reductions in glutamate release could occur are discussed.     

The efficacy and safety of venetoclax therapy in elderly patients with relapsed,refractory chronic lymphocytic leukaemia

Elderly chronic lymphocytic leukaemia (CLL) patients treated outside of trials have notably greater toxicity with the Bruton's tyrosine kinase inhibitor ibrutinib compared to younger patients. It is not known whether the same holds true for the B-cell lymphoma 2 inhibitor venetoclax. We provide a comprehensive analysis of key safety measures and efficacy in 342 patients comparing age categories ≥75 and <75 years treated in the relapsed, refractory non-trial setting. We demonstrate that venetoclax has equivalent efficacy and safety in relapsed/refractory CLL patients who are elderly, the majority of whom are previous ibrutinib-exposed and therefore may otherwise have few clear therapeutic options.     

Pembrolizumab with R-CHOP in previously untreated diffuse large B-cell lymphoma: potential for biomarker driven therapy

Tumor programmed death-ligand 1 (PD-L1) expression in diffuse large B-cell lymphoma (DLBCL) is associated with inferior outcomes. The first-line immunologically-replete setting may be an opportune time for PD-1 inhibition. We evaluated pembrolizumab in combination with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in untreated patients with DLBCL. Eligible patients were age 18 or older, had adequate organ function, and had DLBCL requiring full-course therapy. Patients received pembrolizumab 200 mg/cycle with R-CHOP, primarily to assess toxicity. Response assessment utilized standard criteria, and PD-L1 staining was performed at a validated central laboratory. Among 30 patients, toxicity was comparable to standard R-CHOP but with two grade ≥3 immune related adverse events (rash, pneumonitis). The overall and complete response rate was 90% and 77%. With 25·5 months of median follow-up, 2-year progression-free survival (PFS) is 83%. PD-L1 expression was associated with non-GCB subtype, and improved PFS and survival. Pembrolizumab can safely be added to R-CHOP, and is associated with a high CR rate and 2-year PFS. Improved PFS with PR-CHOP in PD-L1 expressing tumors contradicts historical data in R-CHOP treated patients, supporting evaluation of PD-L1 as a biomarker to identify DLBCL patients who may benefit from this first-line strategy.     

Predominant endothelial vasomotor activity during human sleep: a near‐infrared spectroscopy study

Vasomotion is important in the study of vascular disorders, including stroke. Spontaneous low and very low hemodynamic oscillations (3–150 mHz) measured with near‐infrared spectroscopy (NIRS) reflect the endothelial (3–20 mHz), neurogenic (20–40 mHz) and myogenic (40–150 mHz) components of vasomotion. We investigated sleep‐specific patterns of vasomotion by characterizing hemodynamic oscillations with NIRS in healthy subjects, and tested the feasibility of NIRS as a bedside tool for monitoring vasomotion during whole‐night sleep. To characterize local cerebral vasomotion, we compared cerebral NIRS measurements with muscular NIRS measurements and peripheral arterial oxygen saturation (SpO₂) during different sleep stages in 14 healthy volunteers. Spectral powers of hemodynamic oscillations in the frequency range of endothelial vasomotion were systemically predominant in every sleep stage, and the powers of endothelial and neurogenic vasomotion decreased in deep sleep as compared with light sleep and rapid eye movement (REM) sleep in brain, muscle, and SpO₂. The decrease in the powers of myogenic vasomotion in deep sleep only occurred in brain, and not in muscle. These results point to a predominant role of endothelial function in regulating vasomotion during sleep. The decline in cerebral endothelial and neurogenic vasomotion during progression to deeper non‐REM sleep suggests that deep sleep may play a protective role for vascular function. NIRS can be used to monitor endothelial control of vasomotion during nocturnal sleep, thus providing a promising non‐invasive bedside tool with which to study the sleep‐relevant pathological mechanisms in vascular diseases and stroke.